7-73669495-G-A

Variant summary

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

The ENST00000324941.5(VPS37D):​c.215G>A​(p.Arg72Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,580,544 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000046 ( 1 hom. )

Consequence

VPS37D
ENST00000324941.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
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=0.11525446).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VPS37DNM_001077621.2 linkuse as main transcriptc.215G>A p.Arg72Gln missense_variant 2/4 ENST00000324941.5 NP_001071089.1 Q86XT2
VPS37DXM_017011779.2 linkuse as main transcriptc.92G>A p.Arg31Gln missense_variant 2/4 XP_016867268.1
VPS37DXM_047419927.1 linkuse as main transcriptc.-14G>A 5_prime_UTR_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.215G>A p.Arg72Gln missense_variant 2/41 NM_001077621.2 ENSP00000320416.4 Q86XT2
VPS37DENST00000451519.1 linkuse as main transcriptc.138+1399G>A intron_variant 5 ENSP00000413337.1 C9JYT9

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152248
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000106
AC:
2
AN:
187910
Hom.:
0
AF XY:
0.00000979
AC XY:
1
AN XY:
102178
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:
0.0000398
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000125
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000455
AC:
65
AN:
1428296
Hom.:
1
Cov.:
31
AF XY:
0.0000269
AC XY:
19
AN XY:
707612
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:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000557
Gnomad4 OTH exome
AF:
0.0000339
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152248
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000167
AC:
2

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 GeneticsJan 31, 2022The c.215G>A (p.R72Q) alteration is located in exon 2 (coding exon 2) of the VPS37D gene. This alteration results from a G to A substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a glutamine (Q). 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
0.16
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
27
DANN
Benign
0.56
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
-0.42
N
MutationTaster
Benign
0.81
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
2.1
N
REVEL
Benign
0.22
Sift
Benign
1.0
T
Sift4G
Benign
0.21
T
Polyphen
0.67
P
Vest4
0.24
MutPred
0.49
Loss of MoRF binding (P = 0.0247);
MVP
0.13
MPC
1.0
ClinPred
0.56
D
GERP RS
4.3
Varity_R
0.077
gMVP
0.30

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: rs782184726; hg19: chr7-73083825; API