NM_018341.3:c.-13G>C

Variant names:

• chr6-169751645-G-C
• rs182293452
• NM_018341.3:c.-13G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018341.3(ERMARD):​c.-13G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,565,666 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (7 hom.)
• Consequence: ERMARD NM_018341.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.521
• Publications: 0 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]

DYNLT2 (HGNC:11695): (dynein light chain Tctex-type 2) Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cytosol and sperm flagellum. Predicted to be extrinsic component of membrane. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-169751645-G-C is Benign according to our data. Variant chr6-169751645-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 384877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 398 AD,Unknown gene.

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.-13G>C		5_prime_UTR	Exon 1 of 18	NP_060811.1	Q5T6L9-1
	ERMARD	NM_001278531.2		c.-13G>C		5_prime_UTR	Exon 1 of 18	NP_001265460.1	Q5T6L9-3
	ERMARD	NM_001278533.2		c.-13G>C		5_prime_UTR	Exon 1 of 17	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.-13G>C		5_prime_UTR	Exon 1 of 18	ENSP00000355735.3	Q5T6L9-1
	ERMARD	ENST00000418781.7	TSL:1	c.-13G>C		5_prime_UTR	Exon 1 of 17	ENSP00000397661.2	Q5T6L9-2
	ERMARD	ENST00000854211.1		c.-13G>C		5_prime_UTR	Exon 1 of 19	ENSP00000524270.1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 399 AN: 152248 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00926

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000605 AC: 103 AN: 170368 AF XY: 0.000480

Gnomad AFR exome AF: 0.00959

Gnomad AMR exome AF: 0.000315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000432

GnomAD4 exome AF: 0.000254 AC: 359 AN: 1413302 Hom.: 7 Cov.: 31 AF XY: 0.000220 AC XY: 154 AN XY: 698982

African (AFR) AF: 0.00949 AC: 306 AN: 32242

American (AMR) AF: 0.000382 AC: 14 AN: 36696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 36886

South Asian (SAS) AF: 0.0000368 AC: 3 AN: 81616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49472

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5568

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1087044

Other (OTH) AF: 0.000530 AC: 31 AN: 58496

GnomAD4 genome AF: 0.00261 AC: 398 AN: 152364 Hom.: 2 Cov.: 33 AF XY: 0.00255 AC XY: 190 AN XY: 74510

African (AFR) AF: 0.00921 AC: 383 AN: 41592

American (AMR) AF: 0.000588 AC: 9 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.0000428 Hom.: 0

Bravo AF: 0.00311

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.52
PhyloP100		0.52
PromoterAI		0.11	Neutral
Mutation Taster		=300/0	polymorphism

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: rs182293452; hg19: chr6-170151741;