7-73671083-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6

The NM_001077621.2(VPS37D):​c.463C>T​(p.Arg155Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,611,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. R155R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

VPS37D
NM_001077621.2 missense

Scores

10
7
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.763
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843
BP6
Variant 7-73671083-C-T is Benign according to our data. Variant chr7-73671083-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2681643.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS37DNM_001077621.2 linkc.463C>T p.Arg155Cys missense_variant Exon 4 of 4 ENST00000324941.5 NP_001071089.1 Q86XT2
VPS37DXM_017011779.2 linkc.340C>T p.Arg114Cys missense_variant Exon 4 of 4 XP_016867268.1
VPS37DXM_047419927.1 linkc.235C>T p.Arg79Cys missense_variant Exon 4 of 4 XP_047275883.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS37DENST00000324941.5 linkc.463C>T p.Arg155Cys missense_variant Exon 4 of 4 1 NM_001077621.2 ENSP00000320416.4 Q86XT2
VPS37DENST00000451519.1 linkc.208C>T p.Arg70Cys missense_variant Exon 2 of 2 5 ENSP00000413337.1 C9JYT9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000210
AC:
5
AN:
238342
Hom.:
0
AF XY:
0.0000229
AC XY:
3
AN XY:
131174
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.000149
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1458954
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
725932
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:
0.0000232
Gnomad4 FIN exome
AF:
0.000137
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000250
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1
-
Department of Clinical Pathology, School of Medicine, Fujita Health University
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.48
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Uncertain
0.57
D
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-7.3
D;D
REVEL
Pathogenic
0.72
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.83
MutPred
0.59
Loss of solvent accessibility (P = 0.0079);.;
MVP
0.88
MPC
1.2
ClinPred
0.99
D
GERP RS
3.3
Varity_R
0.79
gMVP
0.80

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: rs782513824; hg19: chr7-73085413; COSMIC: COSV61446359; API