dbSNP rs147252072: SAMD12:p.Gln36Glu (chr8-118580801-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_207506.3(SAMD12):c.106C>G(p.Gln36Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,612,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SAMD12
NM_207506.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09878555).

BS2

High AC in GnomAd4 at 12 AD gene.

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.106C>G	p.Gln36Glu	missense	Exon 2 of 4	NP_997389.2	Q8N8I0
SAMD12	NM_001101676.2		c.106C>G	p.Gln36Glu	missense	Exon 2 of 5	NP_001095146.1	H0YEJ0
SAMD12	NM_001363274.2		c.106C>G	p.Gln36Glu	missense	Exon 2 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.106C>G	p.Gln36Glu	missense	Exon 2 of 4	ENSP00000314173.4	Q8N8I0
SAMD12	ENST00000526328.6	TSL:1	n.228C>G		non_coding_transcript_exon	Exon 2 of 5
SAMD12	ENST00000964565.1		c.106C>G	p.Gln36Glu	missense	Exon 2 of 4	ENSP00000634624.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250668

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460266

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726468

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33418

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110696

Other (OTH)

AF:

0.0000332

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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

0.078

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

0.028

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Benign

0.0031

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

3.7

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.96

REVEL

Benign

0.057

Sift

Benign

0.64

Sift4G

Benign

0.96

Polyphen

0.030

Vest4

0.25

MVP

0.40

MPC

0.084

ClinPred

0.035

GERP RS

4.4

Varity_R

0.096

gMVP

0.14

Mutation Taster

=74/26

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over