ENST00000741300.1:n.97-5662C>T

Variant names:

• chr8-118138219-G-A
• rs10505328
• ENST00000741300.1:n.97-5662C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000741300.1(ENSG00000296719):​n.97-5662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,970 control chromosomes in the GnomAD database, including 12,861 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 0.39 (12861 hom., cov: 32)
• Consequence: ENSG00000296719 ENST00000741300.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 9 publications found

Genes affected

ENSG00000296719 (HGNC:):

SAMD12 (HGNC:31750): (sterile alpha motif domain containing 12) Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasmic side of plasma membrane. Implicated in familial adult myoclonic epilepsy 1. [provided by Alliance of Genome Resources, Apr 2022]

SAMD12 Gene-Disease associations (from GenCC):

• epilepsy, familial adult myoclonic, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD12	NR_146234.2	n.703-5662C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296719	ENST00000741300.1	n.97-5662C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59021 AN: 151850 Hom.: 12861 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.389 AC: 59041 AN: 151970 Hom.: 12861 Cov.: 32 AF XY: 0.389 AC XY: 28854 AN XY: 74256

African (AFR) AF: 0.193 AC: 8007 AN: 41474

American (AMR) AF: 0.333 AC: 5078 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1779 AN: 3466

East Asian (EAS) AF: 0.496 AC: 2559 AN: 5158

South Asian (SAS) AF: 0.369 AC: 1774 AN: 4814

European-Finnish (FIN) AF: 0.497 AC: 5243 AN: 10542

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33063 AN: 67946

Other (OTH) AF: 0.402 AC: 846 AN: 2102

Alfa AF: 0.440 Hom.: 9446

Bravo AF: 0.373

Asia WGS AF: 0.372 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs10505328; hg19: chr8-119150458;