NM_001191055.2:c.794T>G

Variant names:

• chr19-53050045-T-G
• rs2083905904
• NM_001191055.2:c.794T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001191055.2(ERVV-2):​c.794T>G​(p.Leu265Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,333,378 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: not found (cov: 20)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.308
• Publications: 0 publications found

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]

ZNF702P (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18734607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191055.2. 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
	ERVV-2	NM_001191055.2	MANE Select	c.794T>G	p.Leu265Arg	missense	Exon 2 of 2	NP_001177984.1	B6SEH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERVV-2	ENST00000601417.3	TSL:4 MANE Select	c.794T>G	p.Leu265Arg	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6521A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000450 AC: 6 AN: 1333378 Hom.: 0 Cov.: 32 AF XY: 0.00000456 AC XY: 3 AN XY: 658586

African (AFR) AF: 0.0000668 AC: 2 AN: 29932

American (AMR) AF: 0.00 AC: 0 AN: 34154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24704

East Asian (EAS) AF: 0.00 AC: 0 AN: 35628

South Asian (SAS) AF: 0.00 AC: 0 AN: 76454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33656

Middle Eastern (MID) AF: 0.000546 AC: 3 AN: 5494

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1037256

Other (OTH) AF: 0.00 AC: 0 AN: 56100

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.71
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.19	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.31
PrimateAI	Benign	0.42	T
Sift4G	Pathogenic	0.0	D
Vest4		0.33
MVP		0.42
GERP RS		0.42
Varity_R		0.20
gMVP		0.54
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs2083905904; hg19: chr19-53553298;