chr6-130146067-T-C

Variant names:

• chr6-130146067-T-C
• NM_001017373.4:c.1138A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017373.4(SAMD3):​c.1138A>G​(p.Ile380Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,443,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SAMD3 NM_001017373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14548483).

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.1138A>G	p.Ile380Val	missense	Exon 10 of 12	NP_001017373.2	Q8N6K7-1
	SAMD3	NM_001277185.2		c.1210A>G	p.Ile404Val	missense	Exon 9 of 11	NP_001264114.1	Q8N6K7-3
	SAMD3	NM_001258275.3		c.1138A>G	p.Ile380Val	missense	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.1138A>G	p.Ile380Val	missense	Exon 10 of 12	ENSP00000403565.2	Q8N6K7-1
	SAMD3	ENST00000457563.6	TSL:2	c.1210A>G	p.Ile404Val	missense	Exon 9 of 11	ENSP00000402092.2	Q8N6K7-3
	SAMD3	ENST00000368134.6	TSL:2	c.1138A>G	p.Ile380Val	missense	Exon 12 of 14	ENSP00000357116.2	Q8N6K7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1443916 Hom.: 0 Cov.: 28 AF XY: 0.00000696 AC XY: 5 AN XY: 718162

African (AFR) AF: 0.00 AC: 0 AN: 32686

American (AMR) AF: 0.00 AC: 0 AN: 41476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25708

East Asian (EAS) AF: 0.00 AC: 0 AN: 38866

South Asian (SAS) AF: 0.00 AC: 0 AN: 82256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000634 AC: 7 AN: 1104544

Other (OTH) AF: 0.00 AC: 0 AN: 59612

GnomAD4 genome Cov.: 32

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	Benign	0.067
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.11
Sift	Benign	0.38	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.21	B
Vest4		0.32
MutPred		0.23		Gain of sheet (P = 0.1208)
MVP		0.54
MPC		0.035
ClinPred		0.32	T
GERP RS		4.5
Varity_R		0.082
gMVP		0.16
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr6-130467212;