rs556976940

Variant names:

• chr19-53050129-C-G
• rs556976940
• NM_001191055.2:c.878C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-53050129-C-G
• chr19-53050129-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001191055.2(ERVV-2):​c.878C>G​(p.Thr293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T293M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• 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: 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=0.07332352).

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.878C>G	p.Thr293Arg	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.878C>G	p.Thr293Arg	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6437G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.49e-7 AC: 1 AN: 1335832 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 659940

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30104

American (AMR) AF: 0.0000289 AC: 1 AN: 34632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24742

East Asian (EAS) AF: 0.00 AC: 0 AN: 35642

South Asian (SAS) AF: 0.00 AC: 0 AN: 76594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038770

Other (OTH) AF: 0.00 AC: 0 AN: 56172

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.18
DANN	Benign	0.32
DEOGEN2	Benign	0.0081	T
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.073	T
MutationAssessor	Benign	0.93	L
PhyloP100		-0.66
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.042	D
Vest4		0.15
MVP		0.067
GERP RS		-0.83
Varity_R		0.081
gMVP		0.34
Mutation Taster		=97/3	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: rs556976940; hg19: chr19-53553382;