6-130146180-A-G

Variant names:

• chr6-130146180-A-G
• rs1217324199
• NM_001017373.4:c.1025T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001017373.4(SAMD3):​c.1025T>C​(p.Met342Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000708 in 1,411,596 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SAMD3 NM_001017373.4 missense, splice_region
• Scores: Splicing: ADA: 0.03196
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1025T>C	p.Met342Thr	missense splice_region	Exon 10 of 12	NP_001017373.2	Q8N6K7-1
	SAMD3	NM_001277185.2		c.1097T>C	p.Met366Thr	missense splice_region	Exon 9 of 11	NP_001264114.1	Q8N6K7-3
	SAMD3	NM_001258275.3		c.1025T>C	p.Met342Thr	missense splice_region	Exon 12 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.1025T>C	p.Met342Thr	missense splice_region	Exon 10 of 12	ENSP00000403565.2	Q8N6K7-1
	SAMD3	ENST00000457563.6	TSL:2	c.1097T>C	p.Met366Thr	missense splice_region	Exon 9 of 11	ENSP00000402092.2	Q8N6K7-3
	SAMD3	ENST00000368134.6	TSL:2	c.1025T>C	p.Met342Thr	missense splice_region	Exon 12 of 14	ENSP00000357116.2	Q8N6K7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000466 AC: 1 AN: 214704 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000387

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411596 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 701452

African (AFR) AF: 0.00 AC: 0 AN: 31356

American (AMR) AF: 0.0000269 AC: 1 AN: 37160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24612

East Asian (EAS) AF: 0.00 AC: 0 AN: 37750

South Asian (SAS) AF: 0.00 AC: 0 AN: 76964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088726

Other (OTH) AF: 0.00 AC: 0 AN: 58044

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.039	B
Vest4		0.67
MutPred		0.49		Loss of helix (P = 0.0626)
MVP		0.56
MPC		0.036
ClinPred		0.42	T
GERP RS		5.4
Varity_R		0.39
gMVP		0.49
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.032
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.060		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: rs1217324199; hg19: chr6-130467325;