chr3-36990879-T-C

Position:

• chr3-36990879-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014805.4(EPM2AIP1):​c.*375A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 991,890 control chromosomes in the GnomAD database, including 93,325 homozygotes. 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: 𝑓 0.32 (9824 hom., cov: 32)
  • Exomes 𝑓: 0.44 (83501 hom.)
• Consequence: EPM2AIP1 NM_014805.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

Genes affected

EPM2AIP1 (HGNC:19735): (EPM2A interacting protein 1) The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPM2AIP1	NM_014805.4	c.*375A>G		3_prime_UTR_variant	1/1	ENST00000322716.8	NP_055620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPM2AIP1	ENST00000322716	c.*375A>G		3_prime_UTR_variant	1/1		NM_014805.4	ENSP00000406027.1
EPM2AIP1	ENST00000624586.1	c.388-444A>G		intron_variant		5		ENSP00000485091.1
EPM2AIP1	ENST00000623924.1	c.63-444A>G		intron_variant		5		ENSP00000485489.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49098 AN: 152028 Hom.: 9822 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.440 AC: 369758 AN: 839744 Hom.: 83501 Cov.: 21 AF XY: 0.441 AC XY: 171275 AN XY: 388706

Gnomad4 AFR exome AF: 0.0952

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.0726

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.323 AC: 49104 AN: 152146 Hom.: 9824 Cov.: 32 AF XY: 0.318 AC XY: 23631 AN XY: 74370

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.0776

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.327

Alfa AF: 0.419 Hom.: 13015

Bravo AF: 0.314

Asia WGS AF: 0.173 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.8
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs3172297; hg19: chr3-37032370;