Variant chr6-130146180-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001017373.4(SAMD3):c.1025T>C(p.Met342Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000708 in 1,411,596 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SAMD3
NM_001017373.4 missense, splice_region

Scores

Splicing: ADA: 0.03196

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

Variant links:

Genes affected

SAMD3 (HGNC:21574): (sterile alpha motif domain containing 3)

SAMD3 links:

SAMD3 (HGNC:):

SAMD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD3	NM_001017373.4 linkuse as main transcript	c.1025T>C	p.Met342Thr	missense_variant, splice_region_variant	10/12	ENST00000439090.7	NP_001017373.2	Q8N6K7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD3	ENST00000439090.7 linkuse as main transcript	c.1025T>C	p.Met342Thr	missense_variant, splice_region_variant	10/12	2	NM_001017373.4	ENSP00000403565.2		Q8N6K7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000466

AC:

AN:

214704

Hom.:

AF XY:

0.00

AC XY:

AN XY:

116854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000387

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

7.08e-7

AC:

AN:

1411596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.1025T>C (p.M342T) alteration is located in exon 10 (coding exon 8) of the SAMD3 gene. This alteration results from a T to C substitution at nucleotide position 1025, causing the methionine (M) at amino acid position 342 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;.;T;T

Eigen

Benign

0.048

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

.;T;.;T

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.53

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.039

B;.;B;B

Vest4

0.67

MutPred

0.49

Loss of helix (P = 0.0626);.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);

MVP

0.56

MPC

0.036

ClinPred

0.42

GERP RS

5.4

Varity_R

0.39

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.032

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.060

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