Variant 8-118439834-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2

The NM_207506.3(SAMD12):c.320C>T(p.Thr107Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,612,888 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 23 hom. )

Consequence

SAMD12
NM_207506.3 missense, splice_region

Scores

Splicing: ADA: 0.9998

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.60

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 11: AlphaMissense, BayesDel_noAF, Cadd, dbscSNV1_ADA, dbscSNV1_RF, Eigen, FATHMM_MKL, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP6

Variant 8-118439834-G-A is Benign according to our data. Variant chr8-118439834-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658776.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 575 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD12	NM_207506.3 link	c.320C>T	p.Thr107Ile	missense_variant, splice_region_variant	3/4	ENST00000314727.9	NP_997389.2	Q8N8I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD12	ENST00000314727.9 link	c.320C>T	p.Thr107Ile	missense_variant, splice_region_variant	3/4	1	NM_207506.3	ENSP00000314173.4		Q8N8I0

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

575

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00670

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00350

AC:

878

AN:

251142

Hom.:

AF XY:

0.00355

AC XY:

482

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00539

AC:

7866

AN:

1460616

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

3899

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00636

Gnomad4 OTH exome

AF:

0.00543

GnomAD4 genome

AF:

0.00378

AC:

575

AN:

152272

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00670

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00574

Hom.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00335

AC:

407

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

SAMD12: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.073

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-4.3

D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

1.0

.;D

Vest4

0.91

MVP

0.87

MPC

0.42

ClinPred

0.029

GERP RS

5.7

Varity_R

0.55

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over