rs201831635

Variant names:

• chr6-130144702-C-A
• rs201831635
• NM_001017373.4:c.1381G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-130144702-C-A
• chr6-130144702-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001017373.4(SAMD3):​c.1381G>T​(p.Asp461Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D461N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SAMD3 NM_001017373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

Genes affected

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

ENSG00000227678 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD3	NM_001017373.4	MANE Select	c.1381G>T	p.Asp461Tyr	missense	Exon 12 of 12	NP_001017373.2	Q8N6K7-1
	SAMD3	NM_001277185.2		c.1453G>T	p.Asp485Tyr	missense	Exon 11 of 11	NP_001264114.1	Q8N6K7-3
	SAMD3	NM_001258275.3		c.1381G>T	p.Asp461Tyr	missense	Exon 14 of 14	NP_001245204.1	Q8N6K7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD3	ENST00000439090.7	TSL:2 MANE Select	c.1381G>T	p.Asp461Tyr	missense	Exon 12 of 12	ENSP00000403565.2	Q8N6K7-1
	SAMD3	ENST00000457563.6	TSL:2	c.1453G>T	p.Asp485Tyr	missense	Exon 11 of 11	ENSP00000402092.2	Q8N6K7-3
	SAMD3	ENST00000368134.6	TSL:2	c.1381G>T	p.Asp461Tyr	missense	Exon 14 of 14	ENSP00000357116.2	Q8N6K7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.61		Gain of helix (P = 0.0496)
MVP		0.74
MPC		0.24
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.39
gMVP		0.55
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs201831635; hg19: chr6-130465847;