6-169753606-A-T

Variant names:

• chr6-169753606-A-T
• rs2274953
• NM_018341.3:c.7-258A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018341.3(ERMARD):​c.7-258A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERMARD NM_018341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• periventricular nodular heterotopia

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• periventricular nodular heterotopia 6

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018341.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMARD	NM_018341.3	MANE Select	c.7-258A>T		intron	N/A	NP_060811.1	Q5T6L9-1
	ERMARD	NM_001278531.2		c.7-258A>T		intron	N/A	NP_001265460.1	Q5T6L9-3
	ERMARD	NM_001278533.2		c.7-258A>T		intron	N/A	NP_001265462.1	Q5T6L9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERMARD	ENST00000366773.8	TSL:2 MANE Select	c.7-258A>T		intron	N/A	ENSP00000355735.3	Q5T6L9-1
	ERMARD	ENST00000418781.7	TSL:1	c.7-258A>T		intron	N/A	ENSP00000397661.2	Q5T6L9-2
	ERMARD	ENST00000854211.1		c.7-258A>T		intron	N/A	ENSP00000524270.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		1.4

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

Other links and lift over

dbSNP: rs2274953; hg19: chr6-170153702;