7-73669480-A-T

Variant names:

• chr7-73669480-A-T
• rs782491581
• NM_001077621.2:c.200A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001077621.2(VPS37D):​c.200A>T​(p.Glu67Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000183 in 1,582,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: VPS37D NM_001077621.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.200A>T	p.Glu67Val	missense	Exon 2 of 4	NP_001071089.1	Q86XT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37D	ENST00000324941.5	TSL:1 MANE Select	c.200A>T	p.Glu67Val	missense	Exon 2 of 4	ENSP00000320416.4	Q86XT2
	VPS37D	ENST00000965880.1		c.200A>T	p.Glu67Val	missense	Exon 2 of 4	ENSP00000635939.1
	VPS37D	ENST00000903466.1		c.200A>T	p.Glu67Val	missense	Exon 2 of 4	ENSP00000573525.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000103 AC: 2 AN: 195040 AF XY: 0.0000188

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000239

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000196 AC: 28 AN: 1430792 Hom.: 0 Cov.: 31 AF XY: 0.0000282 AC XY: 20 AN XY: 709092

African (AFR) AF: 0.00 AC: 0 AN: 32772

American (AMR) AF: 0.00 AC: 0 AN: 40204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25530

East Asian (EAS) AF: 0.00 AC: 0 AN: 37994

South Asian (SAS) AF: 0.00 AC: 0 AN: 81976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.0000237 AC: 26 AN: 1097100

Other (OTH) AF: 0.0000338 AC: 2 AN: 59120

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	0.0048	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.60
Sift	Benign	0.056	T
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.36
MVP		0.19
MPC		1.1
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.19
gMVP		0.41
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782491581; hg19: chr7-73083810;