Variant 19-53050264-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001191055.2(ERVV-2):c.1013C>T(p.Pro338Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 145,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ERVV-2
NM_001191055.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.305

Variant links:

Genes affected

ERVV-2 (HGNC:39051): (endogenous retrovirus group V member 2, envelope) Many different human endogenous retrovirus (HERV) families are expressed in normal placental tissue at high levels, suggesting that HERVs are functionally important in reproduction. This gene is part of an HERV provirus on human chromosome 19 that has inactivating mutations in the gag and pol genes. This envelope glycoprotein gene appears to have been selectively preserved. The gene's protein product is expressed in the placenta and acts as a syncytin in Old World monkeys, but has lost the fusogenic activity in humans and other primate lineages. [provided by RefSeq, Jun 2015]

ERVV-2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20671296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERVV-2	NM_001191055.2 linkuse as main transcript	c.1013C>T	p.Pro338Leu	missense_variant	2/2	ENST00000601417.3	NP_001177984.1	B6SEH9M9QSX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3 linkuse as main transcript	c.1013C>T	p.Pro338Leu	missense_variant	2/2	4	NM_001191055.2	ENSP00000472919.1		B6SEH9

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

150

AN:

145752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000444

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000139

AC:

AN:

646056

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

342982

show subpopulations

Gnomad4 AFR exome

AF:

0.00530

Gnomad4 AMR exome

AF:

0.000146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000897

GnomAD4 genome

AF:

0.00104

AC:

151

AN:

145864

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

71180

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.000340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000217

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000444

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00110

Hom.:

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 submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.1013C>T (p.P338L) alteration is located in exon 2 (coding exon 1) of the ERVV-2 gene. This alteration results from a C to T substitution at nucleotide position 1013, causing the proline (P) at amino acid position 338 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.0066

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.57

M_CAP

Benign

0.021

MetaRNN

Benign

0.21

MutationAssessor

Benign

0.76

PrimateAI

Benign

0.42

Sift4G

Pathogenic

0.0

Vest4

0.31

MVP

0.49

GERP RS

0.42

Varity_R

0.081

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over