17-3494408-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000049.4(ASPA):c.693C>T(p.Tyr231Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,609,446 control chromosomes in the GnomAD database, including 69,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5840 hom., cov: 32)

Exomes 𝑓: 0.29 ( 63740 hom. )

Consequence

ASPA
NM_000049.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.453

Publications

43 publications found

Variant links:

Genes affected

ASPA (HGNC:756): (aspartoacylase) This gene encodes an enzyme that catalyzes the conversion of N-acetyl_L-aspartic acid (NAA) to aspartate and acetate. NAA is abundant in the brain where hydrolysis by aspartoacylase is thought to help maintain white matter. This protein is an NAA scavenger in other tissues. Mutations in this gene cause Canavan disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ASPA links:

SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

SPATA22 Gene-Disease associations (from GenCC):

infertility disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

SPATA22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 17-3494408-C-T is Benign according to our data. Variant chr17-3494408-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 197621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.453 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPA	NM_000049.4 link	c.693C>T	p.Tyr231Tyr	synonymous_variant	Exon 5 of 6	ENST00000263080.3	NP_000040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ASPA	ENST00000263080.3 link	c.693C>T	p.Tyr231Tyr	synonymous_variant	Exon 5 of 6	1	NM_000049.4	ENSP00000263080.2
ASPA	ENST00000456349.6 link	c.693C>T	p.Tyr231Tyr	synonymous_variant	Exon 6 of 7	1		ENSP00000409976.2
SPATA22	ENST00000541913.5 link	c.-74+19004G>A		intron_variant	Intron 1 of 8	2		ENSP00000441920.1
SPATA22	ENST00000570318.1 link	c.-74+19203G>A		intron_variant	Intron 1 of 1	2		ENSP00000459147.1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40950

AN:

151918

Hom.:

5841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.269

GnomAD2 exomes

AF:

0.260

AC:

65267

AN:

251370

AF XY:

0.263

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.0444

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.289

AC:

421404

AN:

1457410

Hom.:

63740

Cov.:

AF XY:

0.288

AC XY:

208910

AN XY:

725364

show subpopulations

African (AFR)

AF:

0.238

AC:

7961

AN:

33388

American (AMR)

AF:

0.195

AC:

8701

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7400

AN:

26090

East Asian (EAS)

AF:

0.0432

AC:

1713

AN:

39684

South Asian (SAS)

AF:

0.215

AC:

18549

AN:

86198

European-Finnish (FIN)

AF:

0.330

AC:

17619

AN:

53366

Middle Eastern (MID)

AF:

0.250

AC:

1440

AN:

5760

European-Non Finnish (NFE)

AF:

0.308

AC:

341380

AN:

1108000

Other (OTH)

AF:

0.276

AC:

16641

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

14980

29960

44941

59921

74901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10870

21740

32610

43480

54350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.269

AC:

40958

AN:

152036

Hom.:

5840

Cov.:

AF XY:

0.267

AC XY:

19823

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.237

AC:

9828

AN:

41468

American (AMR)

AF:

0.216

AC:

3304

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

995

AN:

3468

East Asian (EAS)

AF:

0.0475

AC:

246

AN:

5184

South Asian (SAS)

AF:

0.208

AC:

1004

AN:

4816

European-Finnish (FIN)

AF:

0.323

AC:

3415

AN:

10558

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21298

AN:

67950

Other (OTH)

AF:

0.266

AC:

560

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1532

3063

4595

6126

7658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

4130

Bravo

AF:

0.258

Asia WGS

AF:

0.135

AC:

470

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.306

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spongy degeneration of central nervous system

Benign:5

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 23, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Benign:1

Apr 10, 2017

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.5

(source)

DANN

Benign

0.72

PhyloP100

0.45

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over