Variant 6-169751662-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2

The NM_018341.3(ERMARD):c.5A>T(p.Glu2Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,559,082 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

ERMARD
NM_018341.3 missense, splice_region

Scores

Splicing: ADA: 0.9993

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.223

Variant links:

Genes affected

ERMARD (HGNC:21056): (ER membrane associated RNA degradation) The protein encoded by this gene contains 2 transmembrane domains near the C-terminus and is localized in the endoplasmic reticulum. Knockout of this gene in developing rat brain showed that it may be involved in neuronal migration. Mutations in this gene are associated with periventricular nodular heterotopia-6 (PVNH6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

ERMARD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

BP6

Variant 6-169751662-A-T is Benign according to our data. Variant chr6-169751662-A-T is described in ClinVar as [Benign]. Clinvar id is 507371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERMARD	NM_018341.3 linkuse as main transcript	c.5A>T	p.Glu2Val	missense_variant, splice_region_variant	1/18	ENST00000366773.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERMARD	ENST00000366773.8 linkuse as main transcript	c.5A>T	p.Glu2Val	missense_variant, splice_region_variant	1/18	2	NM_018341.3	P2	Q5T6L9-1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

593

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.000795

AC:

130

AN:

163514

Hom.:

AF XY:

0.000640

AC XY:

AN XY:

87474

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000682

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000309

Gnomad OTH exome

AF:

0.000446

GnomAD4 exome

AF:

0.000376

AC:

529

AN:

1406798

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

230

AN XY:

695088

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00390

AC:

594

AN:

152284

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0135

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.00466

ESP6500AA

AF:

0.0110

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000813

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 02, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.0096

.;T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.39

T;T;T;T

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-2.0

N;N;.;N

REVEL

Benign

0.045

Sift

Uncertain

0.0050

D;D;.;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.28, 0.72

.;B;.;P

Vest4

0.39

MVP

0.35

MPC

0.10

ClinPred

0.064

GERP RS

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.83

SpliceAI score (max)

0.50

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.50

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over