Variant 7-73671206-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 NM_001077621.2(VPS37D):c.586G>A(p.Ala196Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VPS37D
NM_001077621.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

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:

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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=0.19964117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VPS37D	NM_001077621.2 linkuse as main transcript	c.586G>A	p.Ala196Thr	missense_variant	4/4	ENST00000324941.5	NP_001071089.1
VPS37D	XM_017011779.2 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant	4/4		XP_016867268.1
VPS37D	XM_047419927.1 linkuse as main transcript	c.358G>A	p.Ala120Thr	missense_variant	4/4		XP_047275883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37D	ENST00000324941.5 linkuse as main transcript	c.586G>A	p.Ala196Thr	missense_variant	4/4	1	NM_001077621.2	ENSP00000320416	P1
VPS37D	ENST00000451519.1 linkuse as main transcript	c.331G>A	p.Ala111Thr	missense_variant	2/2	5		ENSP00000413337

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713270

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 04, 2024

The c.586G>A (p.A196T) alteration is located in exon 4 (coding exon 4) of the VPS37D gene. This alteration results from a G to A substitution at nucleotide position 586, causing the alanine (A) at amino acid position 196 to be replaced by a threonine (T). 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

Benign

0.078

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.96

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.11

Sift

Benign

0.098

T;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;.

Vest4

0.20

MutPred

0.34

Gain of glycosylation at A196 (P = 0.0053);.;

MVP

0.12

MPC

0.93

ClinPred

0.74

GERP RS

4.1

Varity_R

0.068

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over