NM_152703.5:c.303G>C

Variant names:

• chr7-93135669-C-G
• rs1133906
• NM_152703.5:c.303G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q101Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD9L NM_152703.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 18 publications found

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]

SAMD9L Gene-Disease associations (from GenCC):

• ataxia-pancytopenia syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• spinocerebellar ataxia 49

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152703.5. 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
	SAMD9L	NM_152703.5	MANE Select	c.303G>C	p.Gln101His	missense	Exon 5 of 5	NP_689916.2
	SAMD9L	NM_001303496.3		c.303G>C	p.Gln101His	missense	Exon 5 of 5	NP_001290425.1
	SAMD9L	NM_001303497.3		c.303G>C	p.Gln101His	missense	Exon 6 of 6	NP_001290426.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD9L	ENST00000318238.9	TSL:1 MANE Select	c.303G>C	p.Gln101His	missense	Exon 5 of 5	ENSP00000326247.4
	SAMD9L	ENST00000414791.6	TSL:1	c.303G>C	p.Gln101His	missense	Exon 2 of 2	ENSP00000396137.2
	SAMD9L	ENST00000437805.5	TSL:1	c.303G>C	p.Gln101His	missense	Exon 6 of 6	ENSP00000408796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 11385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-1.5
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.058
Sift	Benign	0.13	T
Sift4G	Benign	0.075	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.065		Gain of ubiquitination at K105 (P = 0.0737)
MVP		0.13
MPC		0.17
ClinPred		0.046	T
GERP RS		0.63
PromoterAI		-0.0026	Neutral
Varity_R		0.029
gMVP		0.25
Mutation Taster		=100/0	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: rs1133906; hg19: chr7-92764982;