Genetic Variant SAMD12:c.*247G>A (chr8-118379170-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207506.3(SAMD12):c.*247G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 1,227,446 control chromosomes in the GnomAD database, including 2,789 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 0.054 ( 482 hom., cov: 33)

Exomes 𝑓: 0.061 ( 2307 hom. )

Consequence

SAMD12
NM_207506.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

Publications

7 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:

ENSG00000225885 (HGNC:):

ENSG00000225885 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SAMD12	NM_207506.3	MANE Select	c.*247G>A	3_prime_UTR	Exon 4 of 4	NP_997389.2	Q8N8I0
SAMD12	NM_001101676.2		c.463+390G>A	intron	N/A	NP_001095146.1	H0YEJ0
SAMD12	NM_001363274.2		c.463+390G>A	intron	N/A	NP_001350203.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SAMD12	ENST00000314727.9	TSL:1 MANE Select	c.*247G>A	3_prime_UTR	Exon 4 of 4	ENSP00000314173.4	Q8N8I0
SAMD12	ENST00000526328.6	TSL:1	n.585+390G>A	intron	N/A
SAMD12	ENST00000964565.1		c.*247G>A	3_prime_UTR	Exon 4 of 4	ENSP00000634624.1

Frequencies

GnomAD3 genomes

AF:

0.0538

AC:

8181

AN:

152126

Hom.:

480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.0368

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0584

Gnomad OTH

AF:

0.0583

GnomAD4 exome

AF:

0.0606

AC:

65119

AN:

1075202

Hom.:

2307

Cov.:

AF XY:

0.0605

AC XY:

30720

AN XY:

508158

show subpopulations

African (AFR)

AF:

0.00840

AC:

207

AN:

24654

American (AMR)

AF:

0.201

AC:

2236

AN:

11124

Ashkenazi Jewish (ASJ)

AF:

0.0419

AC:

576

AN:

13758

East Asian (EAS)

AF:

0.000460

AC:

AN:

26080

South Asian (SAS)

AF:

0.0359

AC:

943

AN:

26298

European-Finnish (FIN)

AF:

0.0403

AC:

630

AN:

15644

Middle Eastern (MID)

AF:

0.0283

AC:

AN:

2796

European-Non Finnish (NFE)

AF:

0.0637

AC:

58073

AN:

912010

Other (OTH)

AF:

0.0552

AC:

2363

AN:

42838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2663

5326

7988

10651

13314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2560

5120

7680

10240

12800

<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:

0.0538

AC:

8187

AN:

152244

Hom.:

482

Cov.:

AF XY:

0.0550

AC XY:

4097

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0126

AC:

525

AN:

41554

American (AMR)

AF:

0.187

AC:

2857

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3466

East Asian (EAS)

AF:

0.00135

AC:

AN:

5178

South Asian (SAS)

AF:

0.0302

AC:

146

AN:

4830

European-Finnish (FIN)

AF:

0.0368

AC:

390

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0584

AC:

3975

AN:

68024

Other (OTH)

AF:

0.0577

AC:

122

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

380

761

1141

1522

1902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0567

Hom.:

644

Bravo

AF:

0.0625

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.27

(source)

DANN

Benign

0.71

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(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

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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