chr17-3498977-C-T

Position:

chr17-3498977-C-T

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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=-0.81).

BP6

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

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPA	NM_000049.4 linkuse as main transcript	c.831C>T	p.Thr277Thr	synonymous_variant	6/6	ENST00000263080.3	NP_000040.1	P45381Q6FH48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASPA	ENST00000263080.3 linkuse as main transcript	c.831C>T	p.Thr277Thr	synonymous_variant	6/6	1	NM_000049.4	ENSP00000263080.2	P45381
ASPA	ENST00000456349.6 linkuse as main transcript	c.831C>T	p.Thr277Thr	synonymous_variant	7/7	1		ENSP00000409976.2	P45381
SPATA22	ENST00000541913.5 linkuse as main transcript	c.-74+14435G>A		intron_variant		2		ENSP00000441920.1	F5GWB9
SPATA22	ENST00000570318.1 linkuse as main transcript	c.-74+14634G>A		intron_variant		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

GnomAD3 exomes

AF:

0.00632

AC:

1589

AN:

251312

Hom.:

AF XY:

0.00507

AC XY:

688

AN XY:

135834

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 SAS exome

AF:

0.000556

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

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.0393

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00693

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00382

AC:

581

AN:

152264

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

345

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0112

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000275

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 30, 2015	- -

Spongy degeneration of central nervous system

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jun 13, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2022

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.044

DANN

Benign

0.87

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