rs13255144

Variant names:

• chr8-118434776-T-C
• rs13255144
• NM_207506.3:c.322+5056A>G

Variant summary

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

The NM_207506.3(SAMD12):​c.322+5056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,294 control chromosomes in the GnomAD database, including 26,674 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 0.58 (26674 hom., cov: 31)
• Consequence: SAMD12 NM_207506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• Publications: 3 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, SD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207506.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD12	NM_207506.3	MANE Select	c.322+5056A>G		intron	N/A	NP_997389.2	Q8N8I0
	SAMD12	NM_001101676.2		c.322+5056A>G		intron	N/A	NP_001095146.1	H0YEJ0
	SAMD12	NM_001363274.2		c.322+5056A>G		intron	N/A	NP_001350203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD12	ENST00000314727.9	TSL:1 MANE Select	c.322+5056A>G		intron	N/A	ENSP00000314173.4	Q8N8I0
	SAMD12	ENST00000526328.6	TSL:1	n.444+5056A>G		intron	N/A
	SAMD12	ENST00000964565.1		c.292+5086A>G		intron	N/A	ENSP00000634624.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88071 AN: 151178 Hom.: 26667 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.582 AC: 88102 AN: 151294 Hom.: 26674 Cov.: 31 AF XY: 0.586 AC XY: 43301 AN XY: 73906

African (AFR) AF: 0.421 AC: 17388 AN: 41268

American (AMR) AF: 0.662 AC: 10075 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2312 AN: 3460

East Asian (EAS) AF: 0.480 AC: 2456 AN: 5118

South Asian (SAS) AF: 0.609 AC: 2915 AN: 4790

European-Finnish (FIN) AF: 0.664 AC: 6966 AN: 10494

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44008 AN: 67636

Other (OTH) AF: 0.596 AC: 1259 AN: 2114

Alfa AF: 0.603 Hom.: 9477

Bravo AF: 0.576

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.9
DANN	Benign	0.45
PhyloP100		0.60
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: rs13255144; hg19: chr8-119447015;