Genetic Variant ERVV-1:p.Tyr59Asn (chr19-53014265-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152473.3(ERVV-1):c.175T>A(p.Tyr59Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 17)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ERVV-1
NM_152473.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302

Publications

0 publications found

Variant links:

Genes affected

ERVV-1 (HGNC:26501): (endogenous retrovirus group V 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 an HERV provirus on human chromosome 19 that has inactivating mutations in the gag and pol genes. The gene's envelope protein is expressed in the human placenta but is truncated at its C-terminus. [provided by RefSeq, Oct 2015]

ERVV-1 links:

ZNF702P (HGNC:):

ZNF702P links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.132795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVV-1	NM_152473.3 link	c.175T>A	p.Tyr59Asn	missense_variant	Exon 1 of 1	ENST00000602168.2	NP_689686.2	B6SEH8M9QQA5
LOC124904758	XR_007067327.1 link	n.115-5614A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERVV-1	ENST00000602168.2 link	c.175T>A	p.Tyr59Asn	missense_variant	Exon 1 of 1	6	NM_152473.3	ENSP00000473153.1		B6SEH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000198

AC:

AN:

1011140

Hom.:

Cov.:

AF XY:

0.00000198

AC XY:

AN XY:

504402

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

21906

American (AMR)

AF:

0.00

AC:

AN:

25450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19068

East Asian (EAS)

AF:

0.00

AC:

AN:

33414

South Asian (SAS)

AF:

0.00

AC:

AN:

58582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3452

European-Non Finnish (NFE)

AF:

0.00000258

AC:

AN:

773886

Other (OTH)

AF:

0.00

AC:

AN:

44586

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.175T>A (p.Y59N) alteration is located in exon 1 (coding exon 1) of the ERVV-1 gene. This alteration results from a T to A substitution at nucleotide position 175, causing the tyrosine (Y) at amino acid position 59 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0066

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.64

M_CAP

Benign

0.0079

MetaRNN

Benign

0.13

MutationAssessor

Benign

0.34

PhyloP100

0.30

PrimateAI

Uncertain

0.57

Sift4G

Pathogenic

0.0

Vest4

0.40

MVP

0.33

GERP RS

0.23

PromoterAI

0.021

Neutral

(source)

Varity_R

0.13

gMVP

0.069

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr19-53014265-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over