Genetic Variant NM_001077621.2:c.449C>T (chr7-73671069-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.449C>T(p.Ala150Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,714 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 (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

VPS37D
NM_001077621.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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=0.20499107).

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.449C>T	p.Ala150Val	missense	Exon 4 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.449C>T	p.Ala150Val	missense	Exon 4 of 4	ENSP00000320416.4	Q86XT2
VPS37D	ENST00000965880.1		c.446C>T	p.Ala149Val	missense	Exon 4 of 4	ENSP00000635939.1
VPS37D	ENST00000903466.1		c.443C>T	p.Ala148Val	missense	Exon 4 of 4	ENSP00000573525.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000416

AC:

AN:

240360

AF XY:

0.00000757

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459714

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.0000224

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111714

Other (OTH)

AF:

0.00

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

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

Cov.:

ExAC

AF:

0.00000830

AC:

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

Benign

0.11

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.80

M_CAP

Benign

0.042

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.42

MutationAssessor

Benign

-0.14

PhyloP100

1.5

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.35

Sift

Benign

0.43

Sift4G

Benign

0.084

Polyphen

0.99

Vest4

0.12

MutPred

0.63

Loss of helix (P = 0.0237)

MVP

0.20

MPC

0.97

ClinPred

0.91

GERP RS

4.2

Varity_R

0.093

gMVP

0.29

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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