8-118495176-G-C

Variant names:

• chr8-118495176-G-C
• rs4514016
• NM_207506.3:c.193-55215C>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.193-55215C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,164 control chromosomes in the GnomAD database, including 1,257 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 0.12 (1257 hom., cov: 32)
• Consequence: SAMD12 NM_207506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD12	NM_207506.3	MANE Select	c.193-55215C>G		intron	N/A	NP_997389.2
	SAMD12	NM_001101676.2		c.193-55215C>G		intron	N/A	NP_001095146.1
	SAMD12	NM_001363274.2		c.193-55215C>G		intron	N/A	NP_001350203.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD12	ENST00000314727.9	TSL:1 MANE Select	c.193-55215C>G		intron	N/A	ENSP00000314173.4
	SAMD12	ENST00000526328.6	TSL:1	n.315-55215C>G		intron	N/A
	SAMD12	ENST00000524796.6	TSL:3	c.193-55215C>G		intron	N/A	ENSP00000435927.2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18666 AN: 152046 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.123 AC: 18715 AN: 152164 Hom.: 1257 Cov.: 32 AF XY: 0.128 AC XY: 9542 AN XY: 74406

African (AFR) AF: 0.0723 AC: 3002 AN: 41536

American (AMR) AF: 0.134 AC: 2053 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3470

East Asian (EAS) AF: 0.171 AC: 882 AN: 5170

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4822

European-Finnish (FIN) AF: 0.170 AC: 1799 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8802 AN: 67992

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.0593 Hom.: 70

Bravo AF: 0.115

Asia WGS AF: 0.203 AC: 703 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	1.1
DANN	Benign	0.46
PhyloP100		-0.62
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: rs4514016; hg19: chr8-119507415;