6-130154994-T-A

Position:

• chr6-130154994-T-A

Variant summary

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

The NM_001017373.4(SAMD3):​c.854A>T​(p.Asp285Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SAMD3 NM_001017373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41

Genes affected

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

SAMD3 (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.854A>T	p.Asp285Val	missense_variant	9/12	ENST00000439090.7	NP_001017373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD3	ENST00000439090.7	c.854A>T	p.Asp285Val	missense_variant	9/12	2	NM_001017373.4	ENSP00000403565.2
SAMD3	ENST00000457563.6	c.926A>T	p.Asp309Val	missense_variant	8/11	2		ENSP00000402092.2
SAMD3	ENST00000368134.6	c.854A>T	p.Asp285Val	missense_variant	11/14	2		ENSP00000357116.2
SAMD3	ENST00000437477.6	c.854A>T	p.Asp285Val	missense_variant	10/13	5		ENSP00000391163.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461168 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726922

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

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

Jun 10, 2024

The c.854A>T (p.D285V) alteration is located in exon 9 (coding exon 7) of the SAMD3 gene. This alteration results from a A to T substitution at nucleotide position 854, causing the aspartic acid (D) at amino acid position 285 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	0.099
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	.;T;.;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;.;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.12	T;T;T;T
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.66	P;.;P;P
Vest4		0.60
MutPred		0.29		Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.68
MPC		0.059
ClinPred		0.68	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs867745323; hg19: chr6-130476139;