chr6-130144668-G-A

Position:

• chr6-130144668-G-A

Variant summary

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

The NM_001017373.4(SAMD3):​c.1415C>T​(p.Ala472Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAMD3 NM_001017373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66

Genes affected

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

ENSG00000227678 (HGNC:):

ACMG classification

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	c.1415C>T	p.Ala472Val	missense_variant	12/12	ENST00000439090.7	NP_001017373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD3	ENST00000439090.7	c.1415C>T	p.Ala472Val	missense_variant	12/12	2	NM_001017373.4	ENSP00000403565.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 23, 2024

The c.1415C>T (p.A472V) alteration is located in exon 12 (coding exon 10) of the SAMD3 gene. This alteration results from a C to T substitution at nucleotide position 1415, causing the alanine (A) at amino acid position 472 to be replaced by a valine (V). 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	Benign	0.21
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T;T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	.;T;.;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.55	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.17	T;T;T;T
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.29	B;.;B;B
Vest4		0.59
MutPred		0.30		Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.58
MPC		0.12
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.072
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-130465813; COSMIC: COSV62385894; COSMIC: COSV62385894;