rs200330797

Variant names:

• chr6-169751662-A-G
• rs200330797
• NM_018341.3:c.5A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-169751662-A-G
• chr6-169751662-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018341.3(ERMARD):​c.5A>G​(p.Glu2Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,406,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ERMARD NM_018341.3 missense, splice_region
• Scores: Splicing: ADA: 0.9986
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERMARD	NM_018341.3	c.5A>G	p.Glu2Gly	missense_variant, splice_region_variant	Exon 1 of 18	ENST00000366773.8	NP_060811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMARD	ENST00000366773.8	c.5A>G	p.Glu2Gly	missense_variant, splice_region_variant	Exon 1 of 18	2	NM_018341.3	ENSP00000355735.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1406804 Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 2 AN XY: 695088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000555

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: 0.00

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	0.21
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0097	.;T;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.38	T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.;L
PROVEAN	Benign	-2.2	N;N;.;N
REVEL	Benign	0.057
Sift	Uncertain	0.0070	D;D;.;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.28, 0.56	.;B;.;P
Vest4		0.32
MutPred		0.31		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.28
MPC		0.066
ClinPred		0.80	D
GERP RS		-0.67
Varity_R		0.092
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.85
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.46		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs200330797; hg19: chr6-170151758;