dbSNP rs1191422817: VPS37D:p.Arg3Trp (chr7-73667965-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077621.2(VPS37D):c.7C>T(p.Arg3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 146,112 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000022 ( 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: 0.0470

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1417034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077621.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37D	NM_001077621.2	MANE Select	c.7C>T	p.Arg3Trp	missense	Exon 1 of 4	NP_001071089.1	Q86XT2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VPS37D	ENST00000324941.5	TSL:1 MANE Select	c.7C>T	p.Arg3Trp	missense	Exon 1 of 4	ENSP00000320416.4	Q86XT2
VPS37D	ENST00000965880.1		c.7C>T	p.Arg3Trp	missense	Exon 1 of 4	ENSP00000635939.1
VPS37D	ENST00000903466.1		c.7C>T	p.Arg3Trp	missense	Exon 1 of 4	ENSP00000573525.1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000219

AC:

AN:

911222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

428222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17388

American (AMR)

AF:

0.00

AC:

AN:

3256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7246

East Asian (EAS)

AF:

0.00

AC:

AN:

8676

South Asian (SAS)

AF:

0.00

AC:

AN:

18292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2098

European-Non Finnish (NFE)

AF:

0.00000247

AC:

AN:

810836

Other (OTH)

AF:

0.00

AC:

AN:

31768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146112

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71202

show subpopulations

African (AFR)

AF:

0.0000498

AC:

AN:

40126

American (AMR)

AF:

0.00

AC:

AN:

14822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

4936

South Asian (SAS)

AF:

0.00

AC:

AN:

4718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65812

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PhyloP100

0.047

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.85

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.029

Polyphen

0.99

Vest4

0.11

MutPred

0.35

Loss of methylation at R3 (P = 0.0088)

MVP

0.068

MPC

2.0

ClinPred

0.61

GERP RS

1.7

PromoterAI

0.21

Neutral

(source)

Varity_R

0.20

gMVP

0.29

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over