19-53050086-C-A

Variant names:

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

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>A​(p.Pro279Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,458,140 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 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 0.00043 (5 hom., cov: 21)
  • Exomes 𝑓: 0.00028 (38 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=0.0062893927).
• BS2: High Homozygotes in GnomAd4 at 5 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>A	p.Pro279Thr	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>A	p.Pro279Thr	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6480G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000433 AC: 59 AN: 136116 Hom.: 5 Cov.: 21

Gnomad AFR AF: 0.0000274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.000208

Gnomad SAS AF: 0.000497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00162

GnomAD2 exomes AF: 0.000684 AC: 86 AN: 125702 AF XY: 0.000775

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000307

Gnomad ASJ exome AF: 0.00823

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.000260

GnomAD4 exome AF: 0.000281 AC: 371 AN: 1321928 Hom.: 38 Cov.: 33 AF XY: 0.000306 AC XY: 200 AN XY: 652798

African (AFR) AF: 0.0000337 AC: 1 AN: 29714

American (AMR) AF: 0.000353 AC: 12 AN: 33956

Ashkenazi Jewish (ASJ) AF: 0.00839 AC: 206 AN: 24554

East Asian (EAS) AF: 0.0000284 AC: 1 AN: 35200

South Asian (SAS) AF: 0.000213 AC: 16 AN: 75000

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

Middle Eastern (MID) AF: 0.000369 AC: 2 AN: 5418

European-Non Finnish (NFE) AF: 0.0000768 AC: 79 AN: 1028988

Other (OTH) AF: 0.000970 AC: 54 AN: 55650

GnomAD4 genome AF: 0.000433 AC: 59 AN: 136212 Hom.: 5 Cov.: 21 AF XY: 0.000377 AC XY: 25 AN XY: 66336

African (AFR) AF: 0.0000274 AC: 1 AN: 36556

American (AMR) AF: 0.000523 AC: 7 AN: 13374

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 37 AN: 3176

East Asian (EAS) AF: 0.000209 AC: 1 AN: 4786

South Asian (SAS) AF: 0.000499 AC: 2 AN: 4012

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

Middle Eastern (MID) AF: 0.00382 AC: 1 AN: 262

European-Non Finnish (NFE) AF: 0.000113 AC: 7 AN: 61692

Other (OTH) AF: 0.00160 AC: 3 AN: 1878

Alfa AF: 0.000562 Hom.: 23

ExAC AF: 0.000808 AC: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.72
DANN	Benign	0.49
DEOGEN2	Benign	0.0058	T
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0063	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.64
PrimateAI	Benign	0.38	T
Sift4G	Pathogenic	0.0	D
Vest4		0.21
MVP		0.099
GERP RS		0.42
Varity_R		0.051
gMVP		0.33
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;