Genetic Variant ERVFRD-1:p.Ser199Leu (chr6-11104715-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207582.3(ERVFRD-1):c.596C>T(p.Ser199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ERVFRD-1
NM_207582.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.365

Publications

0 publications found

Variant links:

Genes affected

ERVFRD-1 (HGNC:33823): (endogenous retrovirus group FRD member 1, 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 a human endogenous retrovirus provirus on chromosome 6 that has inactivating mutations in the gag and pol genes. This gene is the envelope glycoprotein gene which appears to have been selectively preserved. The gene's protein product plays a major role in placental development and trophoblast fusion. The protein has the characteristics of a typical retroviral envelope protein, including a cleavage site that separates the surface (SU) and transmembrane (TM) proteins which form a heterodimer. [provided by RefSeq, Jun 2012]

ERVFRD-1 links:

SMIM13 (HGNC:27356): (small integral membrane protein 13) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM13 links:

ENSG00000293642 (HGNC:):

ENSG00000293642 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103979886).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207582.3. 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
	ERVFRD-1	NM_207582.3	MANE Select	c.596C>T	p.Ser199Leu	missense	Exon 2 of 2	NP_997465.1	P60508
	SMIM13	NM_001135575.2	MANE Select	c.76+10326G>A		intron	N/A	NP_001129047.1	P0DJ93

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERVFRD-1	ENST00000472091.2	TSL:1 MANE Select	c.596C>T	p.Ser199Leu	missense	Exon 2 of 2	ENSP00000420174.1	P60508
SMIM13	ENST00000416247.4	TSL:1 MANE Select	c.76+10326G>A		intron	N/A	ENSP00000451866.1	P0DJ93
ENSG00000293642	ENST00000716689.1		c.-770+10326G>A		intron	N/A	ENSP00000520595.1	B4DSL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.016

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.61

M_CAP

Benign

0.0019

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.98

PhyloP100

0.36

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.19

REVEL

Benign

0.021

Sift

Uncertain

0.0050

Sift4G

Benign

0.10

Polyphen

0.62

Vest4

0.22

MutPred

0.52

Loss of disorder (P = 0.0127)

MVP

0.14

MPC

0.39

ClinPred

0.17

GERP RS

0.23

Varity_R

0.13

gMVP

0.060

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over