19-53050264-C-T

Variant names:

• chr19-53050264-C-T
• rs1419812165
• NM_001191055.2:c.1013C>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.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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.305
• 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=0.20671296).

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.1013C>T	p.Pro338Leu	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.1013C>T	p.Pro338Leu	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6302G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 150 AN: 145752 Hom.: 0 Cov.: 27

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

GnomAD2 exomes AF: 0.0000722 AC: 9 AN: 124694 AF XY: 0.000103

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.0000424

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000139 AC: 90 AN: 646056 Hom.: 0 Cov.: 8 AF XY: 0.000137 AC XY: 47 AN XY: 342982

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

African (AFR) AF: 0.00530 AC: 82 AN: 15458

American (AMR) AF: 0.000146 AC: 5 AN: 34254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20426

East Asian (EAS) AF: 0.00 AC: 0 AN: 32520

South Asian (SAS) AF: 0.00 AC: 0 AN: 63856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 408396

Other (OTH) AF: 0.0000897 AC: 3 AN: 33430

⚠️ 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 AF: 0.00104 AC: 151 AN: 145864 Hom.: 0 Cov.: 27 AF XY: 0.00108 AC XY: 77 AN XY: 71180

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

African (AFR) AF: 0.00385 AC: 142 AN: 36842

American (AMR) AF: 0.000340 AC: 5 AN: 14722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.000217 AC: 1 AN: 4616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67546

Other (OTH) AF: 0.00 AC: 0 AN: 2022

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0325 Hom.: 42

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.49
DEOGEN2	Benign	0.0066	T
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.21	T
MutationAssessor	Benign	0.76	N
PhyloP100		0.30
PrimateAI	Benign	0.42	T
Sift4G	Pathogenic	0.0	D
Vest4		0.31
MVP		0.49
GERP RS		0.42
Varity_R		0.081
gMVP		0.29
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: rs1419812165; hg19: chr19-53553517;