3-36990879-T-C

Variant names:

• chr3-36990879-T-C
• rs3172297
• NM_014805.4:c.*375A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPM2AIP1	NM_014805.4	c.*375A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000322716.8	NP_055620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPM2AIP1	ENST00000322716.8	c.*375A>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_014805.4	ENSP00000406027.1
EPM2AIP1	ENST00000624586.1	c.388-444A>G		intron_variant	Intron 1 of 1	5		ENSP00000485091.1
EPM2AIP1	ENST00000623924.1	c.63-444A>G		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.0952 AC: 1527 AN: 16042

American (AMR) AF: 0.359 AC: 781 AN: 2176

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 2150 AN: 5396

East Asian (EAS) AF: 0.0726 AC: 305 AN: 4202

South Asian (SAS) AF: 0.243 AC: 4223 AN: 17382

European-Finnish (FIN) AF: 0.372 AC: 204 AN: 548

Middle Eastern (MID) AF: 0.341 AC: 557 AN: 1634

European-Non Finnish (NFE) AF: 0.457 AC: 349221 AN: 764598

Other (OTH) AF: 0.389 AC: 10790 AN: 27766

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

African (AFR) AF: 0.111 AC: 4604 AN: 41538

American (AMR) AF: 0.378 AC: 5772 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3472

East Asian (EAS) AF: 0.0776 AC: 402 AN: 5180

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4820

European-Finnish (FIN) AF: 0.363 AC: 3834 AN: 10552

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30771 AN: 67994

Other (OTH) AF: 0.327 AC: 691 AN: 2114

Alfa AF: 0.408 Hom.: 16182

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
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs3172297; hg19: chr3-37032370;