19-53050086-C-T

Variant names:

• chr19-53050086-C-T
• rs200390313
• NM_001191055.2:c.835C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001191055.2(ERVV-2):​c.835C>T​(p.Pro279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000418 in 1,458,046 control chromosomes in the GnomAD database, including 4 homozygotes. 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. P279A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00023 (1 hom., cov: 21)
  • Exomes 𝑓: 0.000023 (3 hom.)
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02261445).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.835C>T	p.Pro279Ser	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.835C>T	p.Pro279Ser	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6480G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000228 AC: 31 AN: 136116 Hom.: 1 Cov.: 21

Gnomad AFR AF: 0.000659

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000162

Gnomad OTH AF: 0.000539

GnomAD2 exomes AF: 0.0000557 AC: 7 AN: 125702 AF XY: 0.0000439

Gnomad AFR exome AF: 0.000802

Gnomad AMR exome AF: 0.0000438

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 30 AN: 1321930 Hom.: 3 Cov.: 33 AF XY: 0.0000245 AC XY: 16 AN XY: 652800

African (AFR) AF: 0.000606 AC: 18 AN: 29714

American (AMR) AF: 0.00 AC: 0 AN: 33956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24554

East Asian (EAS) AF: 0.0000568 AC: 2 AN: 35200

South Asian (SAS) AF: 0.0000267 AC: 2 AN: 75000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5418

European-Non Finnish (NFE) AF: 0.00000680 AC: 7 AN: 1028990

Other (OTH) AF: 0.0000180 AC: 1 AN: 55650

GnomAD4 genome AF: 0.000228 AC: 31 AN: 136116 Hom.: 1 Cov.: 21 AF XY: 0.000181 AC XY: 12 AN XY: 66228

African (AFR) AF: 0.000659 AC: 24 AN: 36442

American (AMR) AF: 0.000374 AC: 5 AN: 13356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3176

East Asian (EAS) AF: 0.00 AC: 0 AN: 4798

South Asian (SAS) AF: 0.00 AC: 0 AN: 4026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000162 AC: 1 AN: 61700

Other (OTH) AF: 0.000539 AC: 1 AN: 1856

Alfa AF: 0.0000375 Hom.: 23

ExAC AF: 0.0000734 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.3
DANN	Benign	0.46
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.023	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.64
PrimateAI	Benign	0.36	T
Sift4G	Pathogenic	0.0	D
Vest4		0.20
MVP		0.14
GERP RS		0.42
Varity_R		0.031
gMVP		0.34
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: rs200390313; hg19: chr19-53553339;