6-169773331-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018341.3(ERMARD):ā€‹c.1246G>Cā€‹(p.Val416Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V416I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ERMARD
NM_018341.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.551
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.103711784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ERMARDNM_018341.3 linkuse as main transcriptc.1246G>C p.Val416Leu missense_variant 13/18 ENST00000366773.8 NP_060811.1 Q5T6L9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ERMARDENST00000366773.8 linkuse as main transcriptc.1246G>C p.Val416Leu missense_variant 13/182 NM_018341.3 ENSP00000355735.3 Q5T6L9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251342
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461718
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
0.014
DANN
Benign
0.91
DEOGEN2
Benign
0.0088
.;.;T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.77
T;T;T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L;.;L;L;.
MutationTaster
Benign
1.0
N;N;N;N;N
PROVEAN
Benign
-0.82
N;N;N;N;.
REVEL
Benign
0.045
Sift
Benign
0.082
T;D;T;T;.
Sift4G
Benign
0.14
T;D;D;T;D
Polyphen
0.099
B;.;P;B;.
Vest4
0.28
MutPred
0.34
Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);.;
MVP
0.067
MPC
0.061
ClinPred
0.054
T
GERP RS
-4.6
Varity_R
0.035
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.20
Position offset: -12

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.

Other links and lift over

dbSNP: rs143351214; hg19: chr6-170173427; API