6-11105079-A-G

Variant names:

• chr6-11105079-A-G
• rs770816762
• NM_207582.3:c.232T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207582.3(ERVFRD-1):​c.232T>C​(p.Trp78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. W78G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ERVFRD-1 NM_207582.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 0 publications found

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]

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

ENSG00000293642 (HGNC:):

ACMG classification

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=0.24974695).

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.232T>C	p.Trp78Arg	missense	Exon 2 of 2	NP_997465.1	P60508
	SMIM13	NM_001135575.2	MANE Select	c.76+10690A>G		intron	N/A	NP_001129047.1	P0DJ93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERVFRD-1	ENST00000472091.2	TSL:1 MANE Select	c.232T>C	p.Trp78Arg	missense	Exon 2 of 2	ENSP00000420174.1	P60508
	SMIM13	ENST00000416247.4	TSL:1 MANE Select	c.76+10690A>G		intron	N/A	ENSP00000451866.1	P0DJ93
	ENSG00000293642	ENST00000716689.1		c.-770+10690A>G		intron	N/A	ENSP00000520595.1	B4DSL7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.35
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.093
Sift	Benign	0.38	T
Sift4G	Benign	0.085	T
Polyphen		0.49	P
Vest4		0.32
MutPred		0.76		Gain of solvent accessibility (P = 0.0026)
MVP		0.25
MPC		0.86
ClinPred		0.13	T
GERP RS		0.23
Varity_R		0.19
gMVP		0.28
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: rs770816762; hg19: chr6-11105312; COSMIC: COSV65368509;