rs17455085

Variant names:

• chr8-118244617-G-A
• rs17455085
• NM_001101676.2:c.464-46885C>T

Variant summary

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

The NM_001101676.2(SAMD12):​c.464-46885C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,742 control chromosomes in the GnomAD database, including 2,076 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 0.14 (2076 hom., cov: 32)
• Consequence: SAMD12 NM_001101676.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• 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, 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101676.2. 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_001101676.2		c.464-46885C>T		intron	N/A	NP_001095146.1	H0YEJ0
	SAMD12	NM_001349811.2		c.434-46885C>T		intron	N/A	NP_001336740.1	B8ZZB7
	SAMD12	NR_109794.3		n.451-46885C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD12	ENST00000524796.6	TSL:3	c.464-46885C>T		intron	N/A	ENSP00000435927.2	H0YEJ0
	SAMD12	ENST00000409003.5	TSL:5	c.434-46885C>T		intron	N/A	ENSP00000387133.5	B8ZZB7
	SAMD12	ENST00000445741.6	TSL:3	n.*127-4642C>T		intron	N/A	ENSP00000387605.1	F8VYB8

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21063 AN: 151624 Hom.: 2069 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.139 AC: 21090 AN: 151742 Hom.: 2076 Cov.: 32 AF XY: 0.135 AC XY: 10042 AN XY: 74124

African (AFR) AF: 0.278 AC: 11514 AN: 41362

American (AMR) AF: 0.120 AC: 1826 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3466

East Asian (EAS) AF: 0.0956 AC: 490 AN: 5124

South Asian (SAS) AF: 0.0375 AC: 180 AN: 4806

European-Finnish (FIN) AF: 0.0718 AC: 754 AN: 10502

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5772 AN: 67944

Other (OTH) AF: 0.127 AC: 268 AN: 2108

Alfa AF: 0.107 Hom.: 510

Bravo AF: 0.150

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.4
DANN	Benign	0.58
PhyloP100		1.1
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: rs17455085; hg19: chr8-119256856;