19-53050002-C-T

Variant names:

• chr19-53050002-C-T
• rs1419421837
• NM_001191055.2:c.751C>T

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.751C>T​(p.Pro251Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. P251A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 1 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=0.20329937).

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.751C>T	p.Pro251Ser	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.751C>T	p.Pro251Ser	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6564G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000220 AC: 3 AN: 1364684 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 674190

African (AFR) AF: 0.00 AC: 0 AN: 31176

American (AMR) AF: 0.00 AC: 0 AN: 35350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25044

East Asian (EAS) AF: 0.00 AC: 0 AN: 35664

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1062202

Other (OTH) AF: 0.00 AC: 0 AN: 57186

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.30
PrimateAI	Benign	0.37	T
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MVP		0.38
GERP RS		0.42
Varity_R		0.066
gMVP		0.78
Mutation Taster		=99/1	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: rs1419421837; hg19: chr19-53553255;