17-3498977-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000049.4(ASPA):c.831C>T(p.Thr277Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,090 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T277T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0038 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 43 hom. )

Consequence

ASPA
NM_000049.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.20

Publications

4 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=-0.81).

BP6

Variant 17-3498977-C-T is Benign according to our data. Variant chr17-3498977-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00382 (581/152264) while in subpopulation AMR AF = 0.0325 (497/15302). AF 95% confidence interval is 0.0301. There are 16 homozygotes in GnomAd4. There are 345 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPA	NM_000049.4 link	c.831C>T	p.Thr277Thr	synonymous_variant	Exon 6 of 6	ENST00000263080.3	NP_000040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ASPA	ENST00000263080.3 link	c.831C>T	p.Thr277Thr	synonymous_variant	Exon 6 of 6	1	NM_000049.4	ENSP00000263080.2
ASPA	ENST00000456349.6 link	c.831C>T	p.Thr277Thr	synonymous_variant	Exon 7 of 7	1		ENSP00000409976.2
SPATA22	ENST00000541913.5 link	c.-74+14435G>A		intron_variant	Intron 1 of 8	2		ENSP00000441920.1
SPATA22	ENST00000570318.1 link	c.-74+14634G>A		intron_variant	Intron 1 of 1	2		ENSP00000459147.1

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

582

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0115

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00632

AC:

1589

AN:

251312

AF XY:

0.00507

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0386

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00150

AC:

2199

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

986

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33480

American (AMR)

AF:

0.0393

AC:

1759

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00693

AC:

275

AN:

39696

South Asian (SAS)

AF:

0.000417

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111970

Other (OTH)

AF:

0.00149

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

116

232

349

465

581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00382

AC:

581

AN:

152264

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

345

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41542

American (AMR)

AF:

0.0325

AC:

497

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0112

AC:

AN:

5186

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00127

Hom.:

Bravo

AF:

0.00571

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 30, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spongy degeneration of central nervous system

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 13, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 07, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.044

(source)

DANN

Benign

0.87

PhyloP100

-2.2

Mutation Taster

=99/1

polymorphism

(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