Variant 7-73669559-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001077621.2(VPS37D):c.279C>T(p.Ala93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,592,400 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 4 hom., cov: 32)

Exomes 𝑓: 0.011 ( 98 hom. )

Consequence

VPS37D
NM_001077621.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.87

Variant links:

Genes affected

VPS37D (HGNC:18287): (VPS37D subunit of ESCRT-I) Predicted to be involved in protein targeting to membrane; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Located in extracellular exosome. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

VPS37D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 7-73669559-C-T is Benign according to our data. Variant chr7-73669559-C-T is described in ClinVar as [Benign]. Clinvar id is 2579019.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.87 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VPS37D	NM_001077621.2 linkuse as main transcript	c.279C>T	p.Ala93=	synonymous_variant	2/4	ENST00000324941.5	NP_001071089.1
VPS37D	XM_017011779.2 linkuse as main transcript	c.156C>T	p.Ala52=	synonymous_variant	2/4		XP_016867268.1
VPS37D	XM_047419927.1 linkuse as main transcript	c.51C>T	p.Ala17=	synonymous_variant	2/4		XP_047275883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37D	ENST00000324941.5 linkuse as main transcript	c.279C>T	p.Ala93=	synonymous_variant	2/4	1	NM_001077621.2	ENSP00000320416	P1
VPS37D	ENST00000451519.1 linkuse as main transcript	c.139-1455C>T		intron_variant		5		ENSP00000413337

Frequencies

GnomAD3 genomes

AF:

0.00695

AC:

1058

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00706

AC:

1472

AN:

208556

Hom.:

AF XY:

0.00702

AC XY:

795

AN XY:

113248

show subpopulations

Gnomad AFR exome

AF:

0.00205

Gnomad AMR exome

AF:

0.00505

Gnomad ASJ exome

AF:

0.00830

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00303

Gnomad FIN exome

AF:

0.00562

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00608

GnomAD4 exome

AF:

0.0105

AC:

15180

AN:

1440102

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

7368

AN XY:

714088

show subpopulations

Gnomad4 AFR exome

AF:

0.00151

Gnomad4 AMR exome

AF:

0.00476

Gnomad4 ASJ exome

AF:

0.00873

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00327

Gnomad4 FIN exome

AF:

0.00523

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00914

GnomAD4 genome

AF:

0.00695

AC:

1058

AN:

152298

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

506

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00612

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00991

Hom.:

Bravo

AF:

0.00686

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

VPS37D: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.26

DANN

Benign

0.78

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