rs1133906

Positions:

• chr7-93135669-C-G
• chr7-93135669-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152703.5(SAMD9L):​c.303G>C​(p.Gln101His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD9L NM_152703.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

Genes affected

SAMD9L (HGNC:1349): (sterile alpha motif domain containing 9 like) This gene encodes a cytoplasmic protein that acts as a tumor suppressor but also plays a key role in cell proliferation and the innate immune response to viral infection. The encoded protein contains an N-terminal sterile alpha motif domain. Naturally occurring mutations in this gene are associated with myeloid disorders such as juvenile myelomonocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome. Naturally occurring mutations are also associated with hepatitis-B related hepatocellular carcinoma, normophosphatemic familial tumoral calcinosis, and ataxia-pancytopenia syndrome. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05538395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD9L	NM_152703.5	c.303G>C	p.Gln101His	missense_variant	5/5	ENST00000318238.9	NP_689916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMD9L	ENST00000318238.9	c.303G>C	p.Gln101His	missense_variant	5/5	1	NM_152703.5	ENSP00000326247.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.47
DEOGEN2	Benign	0.010	T;T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.26	.;.;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.055	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.14	N;N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	N;N;N;.
REVEL	Benign	0.058
Sift	Benign	0.13	T;T;T;.
Sift4G	Benign	0.075	T;T;T;.
Polyphen		0.0	B;B;B;B
Vest4		0.046
MutPred		0.065		Gain of ubiquitination at K105 (P = 0.0737);Gain of ubiquitination at K105 (P = 0.0737);Gain of ubiquitination at K105 (P = 0.0737);Gain of ubiquitination at K105 (P = 0.0737);
MVP		0.13
MPC		0.17
ClinPred		0.046	T
GERP RS		0.63
Varity_R		0.029
gMVP		0.25

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: rs1133906; hg19: chr7-92764982;