NM_207582.3:c.760G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207582.3(ERVFRD-1):c.760G>A(p.Val254Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,594,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ERVFRD-1
NM_207582.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06694561).

BP6

Variant 6-11104551-C-T is Benign according to our data. Variant chr6-11104551-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3846182.Status of the report is criteria_provided_single_submitter, 1 stars.

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.760G>A	p.Val254Ile	missense	Exon 2 of 2	NP_997465.1	P60508
	SMIM13	NM_001135575.2	MANE Select	c.76+10162C>T		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.760G>A	p.Val254Ile	missense	Exon 2 of 2	ENSP00000420174.1	P60508
SMIM13	ENST00000416247.4	TSL:1 MANE Select	c.76+10162C>T		intron	N/A	ENSP00000451866.1	P0DJ93
ENSG00000293642	ENST00000716689.1		c.-770+10162C>T		intron	N/A	ENSP00000520595.1	B4DSL7

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000186

AC:

AN:

214826

AF XY:

0.0000259

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000619

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1442494

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

715666

show subpopulations

African (AFR)

AF:

0.0000906

AC:

AN:

33110

American (AMR)

AF:

0.00

AC:

AN:

40624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25680

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39182

South Asian (SAS)

AF:

0.000119

AC:

AN:

84268

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000635

AC:

AN:

1101772

Other (OTH)

AF:

0.0000167

AC:

AN:

59744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.070

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.017

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.35

M_CAP

Benign

0.0014

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

PhyloP100

-1.7

PrimateAI

Benign

0.46

PROVEAN

Benign

0.18

REVEL

Benign

0.14

Sift

Benign

0.46

Sift4G

Benign

0.20

Polyphen

0.95

Vest4

0.021

MutPred

0.48

Gain of sheet (P = 0.0477)

MVP

0.040

MPC

0.47

ClinPred

0.30

GERP RS

-0.45

Varity_R

0.048

gMVP

0.089

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over