Variant chr19-35542550-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014364.5(GAPDHS):c.601A>G(p.Met201Val) variant causes a missense change. The variant allele was found at a frequency of 0.000753 in 1,613,982 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 3 hom. )

Consequence

GAPDHS
NM_014364.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.76

Variant links:

Genes affected

GAPDHS (HGNC:24864): (glyceraldehyde-3-phosphate dehydrogenase, spermatogenic) This gene encodes a protein belonging to the glyceraldehyde-3-phosphate dehydrogenase family of enzymes that play an important role in carbohydrate metabolism. Like its somatic cell counterpart, this sperm-specific enzyme functions in a nicotinamide adenine dinucleotide-dependent manner to remove hydrogen and add phosphate to glyceraldehyde 3-phosphate to form 1,3-diphosphoglycerate. During spermiogenesis, this enzyme may play an important role in regulating the switch between different energy-producing pathways, and it is required for sperm motility and male fertility. [provided by RefSeq, Jul 2008]

GAPDHS links:

TMEM147-AS1 (HGNC:51273): (TMEM147 antisense RNA 1)

TMEM147-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011634737).

BP6

Variant 19-35542550-A-G is Benign according to our data. Variant chr19-35542550-A-G is described in ClinVar as [Benign]. Clinvar id is 713729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPDHS	NM_014364.5 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	6/11	ENST00000222286.9
TMEM147-AS1	NR_038396.1 linkuse as main transcript	n.456+361T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPDHS	ENST00000222286.9 linkuse as main transcript	c.601A>G	p.Met201Val	missense_variant	6/11	1	NM_014364.5	P1
TMEM147-AS1	ENST00000589137.5 linkuse as main transcript	n.456+361T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00377

AC:

574

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.000987

AC:

248

AN:

251390

Hom.:

AF XY:

0.000714

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000439

AC:

641

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000359

AC XY:

261

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000844

GnomAD4 genome

AF:

0.00378

AC:

575

AN:

152188

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

272

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.00420

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00119

AC:

145

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-0.020

Eigen_PC

Benign

0.033

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

M;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.020

D;D

Polyphen

0.065

B;.

Vest4

0.24

MVP

0.33

MPC

0.15

ClinPred

0.11

GERP RS

3.9

Varity_R

0.90

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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