7-73669570-C-T

Variant summary

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

The NM_001077621.2(VPS37D):​c.290C>T​(p.Ala97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,592,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

VPS37D
NM_001077621.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.902
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]

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=0.18774968).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VPS37DNM_001077621.2 linkuse as main transcriptc.290C>T p.Ala97Val missense_variant 2/4 ENST00000324941.5 NP_001071089.1
VPS37DXM_017011779.2 linkuse as main transcriptc.167C>T p.Ala56Val missense_variant 2/4 XP_016867268.1
VPS37DXM_047419927.1 linkuse as main transcriptc.62C>T p.Ala21Val missense_variant 2/4 XP_047275883.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VPS37DENST00000324941.5 linkuse as main transcriptc.290C>T p.Ala97Val missense_variant 2/41 NM_001077621.2 ENSP00000320416 P1
VPS37DENST00000451519.1 linkuse as main transcriptc.139-1444C>T intron_variant 5 ENSP00000413337

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152220
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000125
AC:
18
AN:
1439790
Hom.:
0
Cov.:
31
AF XY:
0.0000112
AC XY:
8
AN XY:
713854
show subpopulations
Gnomad4 AFR exome
AF:
0.0000605
Gnomad4 AMR exome
AF:
0.0000480
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000258
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000118
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152220
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000832
AC:
1

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 submitterclinical testingAmbry GeneticsDec 19, 2022The c.290C>T (p.A97V) alteration is located in exon 2 (coding exon 2) of the VPS37D gene. This alteration results from a C to T substitution at nucleotide position 290, causing the alanine (A) at amino acid position 97 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.047
T
Eigen
Benign
-0.071
Eigen_PC
Benign
-0.10
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.80
T
M_CAP
Uncertain
0.099
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.35
Sift
Benign
0.068
T
Sift4G
Benign
0.28
T
Polyphen
0.99
D
Vest4
0.32
MutPred
0.56
Loss of disorder (P = 0.065);
MVP
0.27
MPC
0.83
ClinPred
0.54
D
GERP RS
3.7
Varity_R
0.053
gMVP
0.19

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.

Other links and lift over

dbSNP: rs782081329; hg19: chr7-73083900; API