rs151283330

Variant names:

• chr6-169769642-A-C
• NM_018341.3:c.1162A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-169769642-A-C
• chr6-169769642-A-G
• chr6-169769642-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018341.3(ERMARD):​c.1162A>C​(p.Asn388His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. N388D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ERMARD NM_018341.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06302822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERMARD	NM_018341.3	c.1162A>C	p.Asn388His	missense_variant	Exon 12 of 18	ENST00000366773.8	NP_060811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMARD	ENST00000366773.8	c.1162A>C	p.Asn388His	missense_variant	Exon 12 of 18	2	NM_018341.3	ENSP00000355735.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460650 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726554

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	.;.;T;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.72	T;T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.063	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.;M;M;.
PROVEAN	Benign	-1.7	N;N;N;N;.
REVEL	Benign	0.047
Sift	Benign	0.041	D;T;D;D;.
Sift4G	Benign	0.079	T;T;T;T;T
Polyphen		0.0040	B;.;B;D;.
Vest4		0.17
MutPred		0.23		Loss of helix (P = 0.079);.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;
MVP		0.12
MPC		0.034
ClinPred		0.071	T
GERP RS		-6.7
Varity_R		0.076
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-170169738;