6-169769642-A-G

Position:

chr6-169769642-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018341.3(ERMARD):c.1162A>G(p.Asn388Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,612,910 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 18 hom. )

Consequence

ERMARD
NM_018341.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 0.438

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004989624).

BP6

Variant 6-169769642-A-G is Benign according to our data. Variant chr6-169769642-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 377111.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=2}. Variant chr6-169769642-A-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 418 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERMARD	NM_018341.3 linkuse as main transcript	c.1162A>G	p.Asn388Asp	missense_variant	12/18	ENST00000366773.8	NP_060811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERMARD	ENST00000366773.8 linkuse as main transcript	c.1162A>G	p.Asn388Asp	missense_variant	12/18	2	NM_018341.3	ENSP00000355735	P2	Q5T6L9-1

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00268

AC:

670

AN:

249630

Hom.:

AF XY:

0.00256

AC XY:

345

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000463

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00395

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00417

AC:

6087

AN:

1460622

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

2942

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.00766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000396

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00487

Gnomad4 OTH exome

AF:

0.00401

GnomAD4 genome

AF:

0.00274

AC:

418

AN:

152288

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00416

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00232

AC:

282

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00399

EpiControl

AF:

0.00422

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 16, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ERMARD: BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2018

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. -

ERMARD-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.0

DANN

Benign

0.94

DEOGEN2

Benign

0.015

.;.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.62

T;T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0050

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;.;L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Benign

-2.1

N;N;N;N;.

REVEL

Benign

0.036

Sift

Benign

0.11

T;T;T;T;.

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.0020

B;.;B;B;.

Vest4

0.13

MVP

0.076

MPC

0.036

ClinPred

0.0040

GERP RS

-6.7

Varity_R

0.096

gMVP

0.37

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

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