rs6469756

Variant names:

• chr8-118544191-A-G
• rs6469756
• NM_207506.3:c.192+36524T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-118544191-A-G
• chr8-118544191-A-T

Variant summary

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

The NM_207506.3(SAMD12):​c.192+36524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,168 control chromosomes in the GnomAD database, including 50,492 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 0.81 (50492 hom., cov: 32)
• Consequence: SAMD12 NM_207506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD12	NM_207506.3	c.192+36524T>C		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.192+36524T>C		intron_variant	Intron 2 of 3	1	NM_207506.3	ENSP00000314173.4

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123192 AN: 152050 Hom.: 50431 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.810 AC: 123313 AN: 152168 Hom.: 50492 Cov.: 32 AF XY: 0.809 AC XY: 60180 AN XY: 74370

African (AFR) AF: 0.909 AC: 37756 AN: 41526

American (AMR) AF: 0.831 AC: 12702 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2584 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2785 AN: 5152

South Asian (SAS) AF: 0.797 AC: 3844 AN: 4822

European-Finnish (FIN) AF: 0.791 AC: 8367 AN: 10582

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52777 AN: 68006

Other (OTH) AF: 0.777 AC: 1638 AN: 2108

Alfa AF: 0.798 Hom.: 75323

Bravo AF: 0.817

Asia WGS AF: 0.670 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		-0.13
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: rs6469756; hg19: chr8-119556430;