ENST00000526328.6:n.585+40558A>G

Variant names:

• chr8-118339002-T-C
• rs2450316
• ENST00000526328.6:n.585+40558A>G

Variant summary

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

The ENST00000526328.6(SAMD12):​n.585+40558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,022 control chromosomes in the GnomAD database, including 34,489 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 0.67 (34489 hom., cov: 32)
• Consequence: SAMD12 ENST00000526328.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 1 publications found

Genes affected

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

ENSG00000225885 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD12	NM_001101676.2	c.463+40558A>G		intron_variant	Intron 4 of 4		NP_001095146.1
SAMD12	NM_001349811.2	c.433+40558A>G		intron_variant	Intron 4 of 4		NP_001336740.1
SAMD12	NR_109794.3	n.450+40558A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD12	ENST00000526328.6	n.585+40558A>G		intron_variant	Intron 4 of 4	1
SAMD12	ENST00000524796.6	c.463+40558A>G		intron_variant	Intron 4 of 4	3		ENSP00000435927.2
SAMD12	ENST00000409003.5	c.433+40558A>G		intron_variant	Intron 4 of 4	5		ENSP00000387133.5

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101516 AN: 151904 Hom.: 34436 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.669 AC: 101635 AN: 152022 Hom.: 34489 Cov.: 32 AF XY: 0.673 AC XY: 50036 AN XY: 74318

African (AFR) AF: 0.758 AC: 31436 AN: 41446

American (AMR) AF: 0.712 AC: 10883 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2073 AN: 3464

East Asian (EAS) AF: 0.831 AC: 4302 AN: 5176

South Asian (SAS) AF: 0.696 AC: 3359 AN: 4826

European-Finnish (FIN) AF: 0.656 AC: 6925 AN: 10554

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40695 AN: 67954

Other (OTH) AF: 0.636 AC: 1345 AN: 2114

Alfa AF: 0.613 Hom.: 40191

Bravo AF: 0.675

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.2
DANN	Benign	0.50
PhyloP100		-0.047
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: rs2450316; hg19: chr8-119351241;