chr6-130146105-T-C

Position:

• chr6-130146105-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001017373.4(SAMD3):​c.1100A>G​(p.Glu367Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD3 NM_001017373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

Genes affected

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

ENSG00000227678 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35807294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD3	NM_001017373.4	c.1100A>G	p.Glu367Gly	missense_variant	10/12	ENST00000439090.7	NP_001017373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD3	ENST00000439090.7	c.1100A>G	p.Glu367Gly	missense_variant	10/12	2	NM_001017373.4	ENSP00000403565.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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

Jan 16, 2024

The c.1100A>G (p.E367G) alteration is located in exon 10 (coding exon 8) of the SAMD3 gene. This alteration results from a A to G substitution at nucleotide position 1100, causing the glutamic acid (E) at amino acid position 367 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	.;T;.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M;.;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.4	N;D;N;N
REVEL	Benign	0.12
Sift	Benign	0.055	T;D;T;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.91	P;.;P;P
Vest4		0.38
MutPred		0.45		Loss of stability (P = 0.0356);.;Loss of stability (P = 0.0356);Loss of stability (P = 0.0356);
MVP		0.64
MPC		0.11
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-130467250;