17-3494408-C-T

Position:

chr17-3494408-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000049.4(ASPA):c.693C>T(p.Tyr231=) 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:11

Conservation

PhyloP100: 0.453

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 197621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-3494408-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
ASPA	NM_000049.4 linkuse as main transcript	c.693C>T	p.Tyr231=	synonymous_variant	5/6	ENST00000263080.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ASPA	ENST00000263080.3 linkuse as main transcript	c.693C>T	p.Tyr231=	synonymous_variant	5/6	1	NM_000049.4	P1
ASPA	ENST00000456349.6 linkuse as main transcript	c.693C>T	p.Tyr231=	synonymous_variant	6/7	1		P1
SPATA22	ENST00000541913.5 linkuse as main transcript	c.-74+19004G>A		intron_variant		2
SPATA22	ENST00000570318.1 linkuse as main transcript	c.-74+19203G>A		intron_variant		2

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

GnomAD3 exomes

AF:

0.260

AC:

65267

AN:

251370

Hom.:

9420

AF XY:

0.263

AC XY:

35723

AN XY:

135864

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 SAS exome

AF:

0.219

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

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.0432

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.269

AC:

40958

AN:

152036

Hom.:

5840

Cov.:

AF XY:

0.267

AC XY:

19823

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.0475

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.274

Hom.:

3590

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:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spongy degeneration of central nervous system

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Mar 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 24, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 23, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 10, 2017

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.5

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over