19-53049570-C-G

Position:

• chr19-53049570-C-G

Variant summary

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

The NM_001191055.2(ERVV-2):​c.319C>G​(p.Gln107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 9)
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.305

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.077797204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERVV-2	NM_001191055.2	c.319C>G	p.Gln107Glu	missense_variant	2/2	ENST00000601417.3	NP_001177984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3	c.319C>G	p.Gln107Glu	missense_variant	2/2	4	NM_001191055.2	ENSP00000472919.1

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 7

GnomAD4 genome Cov.: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.319C>G (p.Q107E) alteration is located in exon 2 (coding exon 1) of the ERVV-2 gene. This alteration results from a C to G substitution at nucleotide position 319, causing the glutamine (Q) at amino acid position 107 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.87
DEOGEN2	Benign	0.0034	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.078	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.40	T
Sift4G	Pathogenic	0.0	D
Vest4		0.16
MVP		0.23
GERP RS		0.23
Varity_R		0.15
gMVP		0.034

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-53552823;