rs878855337

Variant names:

• chr7-93132385-C-G
• rs878855337
• NM_152703.5:c.3587G>C

Variant summary

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

The NM_152703.5(SAMD9L):​c.3587G>C​(p.Cys1196Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C1196C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD9L NM_152703.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:2 U:1 O:1
• Conservation: PhyloP100: 7.52
• Publications: 3 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: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD9L	NM_152703.5	c.3587G>C	p.Cys1196Ser	missense_variant	Exon 5 of 5	ENST00000318238.9	NP_689916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD9L	ENST00000318238.9	c.3587G>C	p.Cys1196Ser	missense_variant	Exon 5 of 5	1	NM_152703.5	ENSP00000326247.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:2 Uncertain:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ataxia-pancytopenia syndrome Pathogenic:2 Uncertain:1 Other:1

Jun 06, 2016

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Mar 21, 2025

3billion

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is not observed in the gnomAD v4.1.0 dataset. Predicted Consequence/Location: Missense changes are a common disease-causing mechanism. In silico tool predictions suggest no damaging effect of the variant on gene or gene product [REVEL: 0.24 (<0.4); 3Cnet: 0.02 (<0.1, specificity 0.84 and negative predicitive value 0.97)]. The same nucleotide change resulting in the same amino acid change has been previously reported to be associated with SAMD9L-related disorder (ClinVar ID: VCV000242373 / PMID: 27259050). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 27259050). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline. -

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GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jun 30, 2016

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.032	T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.033
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.69	.;.;T
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;N
PhyloP100		7.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.040	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.0090	B;B;B
Vest4		0.70
MutPred		0.74		Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);
MVP		0.41
MPC		0.25
ClinPred		0.77	D
GERP RS		4.9
Varity_R		0.25
gMVP		0.58
Mutation Taster		=6/94	disease causing (ClinVar)

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: rs878855337; hg19: chr7-92761698;