Variant 7-73667992-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000324941.5(VPS37D):c.34G>A(p.Glu12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000998 in 1,102,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

VPS37D
ENST00000324941.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1131216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37D	NM_001077621.2 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	1/4	ENST00000324941.5	NP_001071089.1	Q86XT2
VPS37D	XM_017011779.2 linkuse as main transcript	c.16-1427G>A		intron_variant			XP_016867268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37D	ENST00000324941.5 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	1/4	1	NM_001077621.2	ENSP00000320416.4		Q86XT2
VPS37D	ENST00000451519.1 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	1/2	5		ENSP00000413337.1		C9JYT9

Frequencies

GnomAD3 genomes

AF:

0.0000673

AC:

AN:

148620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000667

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000105

AC:

AN:

953720

Hom.:

Cov.:

AF XY:

0.00000222

AC XY:

AN XY:

451030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000673

AC:

AN:

148620

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

72416

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.34G>A (p.E12K) alteration is located in exon 1 (coding exon 1) of the VPS37D gene. This alteration results from a G to A substitution at nucleotide position 34, causing the glutamic acid (E) at amino acid position 12 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.67

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.066

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.25

T;T

Polyphen

0.46

P;.

Vest4

0.29

MutPred

0.28

Gain of MoRF binding (P = 0.0017);Gain of MoRF binding (P = 0.0017);

MVP

0.043

MPC

2.1

ClinPred

0.75

GERP RS

1.7

Varity_R

0.20

gMVP

0.25

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