8-118483688-C-T

Variant names:

• chr8-118483688-C-T
• rs2515034
• NM_207506.3:c.193-43727G>A

Variant summary

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

The NM_207506.3(SAMD12):​c.193-43727G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,292 control chromosomes in the GnomAD database, including 67,230 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 0.94 (67230 hom., cov: 32)
• Consequence: SAMD12 NM_207506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 4 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

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 (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD12	NM_207506.3	c.193-43727G>A		intron_variant	Intron 2 of 3	ENST00000314727.9	NP_997389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD12	ENST00000314727.9	c.193-43727G>A		intron_variant	Intron 2 of 3	1	NM_207506.3	ENSP00000314173.4

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142901 AN: 152174 Hom.: 67180 Cov.: 32

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.939 AC: 143009 AN: 152292 Hom.: 67230 Cov.: 32 AF XY: 0.939 AC XY: 69893 AN XY: 74460

African (AFR) AF: 0.954 AC: 39672 AN: 41568

American (AMR) AF: 0.953 AC: 14564 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3191 AN: 3472

East Asian (EAS) AF: 0.805 AC: 4163 AN: 5174

South Asian (SAS) AF: 0.837 AC: 4034 AN: 4822

European-Finnish (FIN) AF: 0.966 AC: 10263 AN: 10622

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63978 AN: 68030

Other (OTH) AF: 0.929 AC: 1961 AN: 2110

Alfa AF: 0.937 Hom.: 44098

Bravo AF: 0.941

Asia WGS AF: 0.804 AC: 2800 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	0.015
DANN	Benign	0.57
PhyloP100		-2.3
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: rs2515034; hg19: chr8-119495927;