dbSNP rs763629042: SAMD12:p.Ser98Cys (chr8-118439862-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207506.3(SAMD12):c.292A>T(p.Ser98Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S98R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SAMD12
NM_207506.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Publications

0 publications found

Variant links:

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

SAMD12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD12	NM_207506.3	MANE Select	c.292A>T	p.Ser98Cys	missense	Exon 3 of 4	NP_997389.2	Q8N8I0
SAMD12	NM_001101676.2		c.292A>T	p.Ser98Cys	missense	Exon 3 of 5	NP_001095146.1	H0YEJ0
SAMD12	NM_001363274.2		c.292A>T	p.Ser98Cys	missense	Exon 3 of 5	NP_001350203.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD12	ENST00000314727.9	TSL:1 MANE Select	c.292A>T	p.Ser98Cys	missense	Exon 3 of 4	ENSP00000314173.4	Q8N8I0
SAMD12	ENST00000526328.6	TSL:1	n.414A>T		non_coding_transcript_exon	Exon 3 of 5
SAMD12	ENST00000524796.6	TSL:3	c.292A>T	p.Ser98Cys	missense	Exon 3 of 5	ENSP00000435927.2	H0YEJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111530

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.60

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.70

PhyloP100

7.7

ClinPred

0.92

GERP RS

5.7

Varity_R

0.36

Mutation Taster

=39/61

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over