19-53050086-C-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062893927).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVV-2	NM_001191055.2	c.835C>A	p.Pro279Thr	missense_variant	Exon 2 of 2	ENST00000601417.3	NP_001177984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3	c.835C>A	p.Pro279Thr	missense_variant	Exon 2 of 2	4	NM_001191055.2	ENSP00000472919.1

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

GnomAD3 exomes AF: 0.000684 AC: 86 AN: 125702 Hom.: 8 AF XY: 0.000775 AC XY: 53 AN XY: 68346

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 SAS exome AF: 0.000342

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

Gnomad4 AFR exome AF: 0.0000337

Gnomad4 AMR exome AF: 0.000353

Gnomad4 ASJ exome AF: 0.00839

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.000213

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000768

Gnomad4 OTH exome AF: 0.000970

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

Gnomad4 AFR AF: 0.0000274

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.0116

Gnomad4 EAS AF: 0.000209

Gnomad4 SAS AF: 0.000499

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00160

Alfa AF: 0.000562 Hom.: 23

ExAC AF: 0.000808 AC: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs200390313; hg19: chr19-53553339;