6-130175981-G-C

Variant names:

• chr6-130175981-G-C
• rs201988282
• NM_001017373.4:c.682C>G

Variant summary

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

The NM_001017373.4(SAMD3):​c.682C>G​(p.Arg228Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R228C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD3 NM_001017373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85
• Publications: 5 publications found

Genes affected

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

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, 0.806

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.682C>G	p.Arg228Gly	missense	Exon 8 of 12	NP_001017373.2	Q8N6K7-1
	SAMD3	NM_001277185.2		c.754C>G	p.Arg252Gly	missense	Exon 7 of 11	NP_001264114.1	Q8N6K7-3
	SAMD3	NM_001258275.3		c.682C>G	p.Arg228Gly	missense	Exon 10 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.682C>G	p.Arg228Gly	missense	Exon 8 of 12	ENSP00000403565.2	Q8N6K7-1
	SAMD3	ENST00000533296.5	TSL:1	n.1359C>G		non_coding_transcript_exon	Exon 7 of 7
	SAMD3	ENST00000457563.6	TSL:2	c.754C>G	p.Arg252Gly	missense	Exon 7 of 11	ENSP00000402092.2	Q8N6K7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.55		Loss of stability (P = 0.0155)
MVP		0.82
MPC		0.26
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.79
Mutation Taster		=81/19	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: rs201988282; hg19: chr6-130497126; COSMIC: COSV100931800;