7-93131118-G-T

Variant names:

• chr7-93131118-G-T
• rs116965992
• NM_152703.5:c.*99C>A

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.*99C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000334 in 599,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: SAMD9L NM_152703.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837
• Publications: 1 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, Orphanet, PanelApp Australia, G2P
• SAMD9L-related spectrum and myeloid neoplasm risk

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• 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 (BayesDel_noAF=-0.91).

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.*99C>A		3_prime_UTR	Exon 5 of 5	NP_689916.2
	SAMD9L	NM_001303496.3		c.*99C>A		3_prime_UTR	Exon 5 of 5	NP_001290425.1	Q8IVG5-1
	SAMD9L	NM_001303497.3		c.*99C>A		3_prime_UTR	Exon 6 of 6	NP_001290426.1	Q8IVG5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD9L	ENST00000318238.9	TSL:1 MANE Select	c.*99C>A		3_prime_UTR	Exon 5 of 5	ENSP00000326247.4	Q8IVG5-1
	SAMD9L	ENST00000437805.5	TSL:1	c.*99C>A		3_prime_UTR	Exon 6 of 6	ENSP00000408796.1	Q8IVG5-1
	SAMD9L	ENST00000411955.5	TSL:5	c.*99C>A		3_prime_UTR	Exon 6 of 6	ENSP00000405760.1	Q8IVG5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000334 AC: 2 AN: 599306 Hom.: 0 Cov.: 8 AF XY: 0.00000329 AC XY: 1 AN XY: 303738

African (AFR) AF: 0.00 AC: 0 AN: 13524

American (AMR) AF: 0.00 AC: 0 AN: 13480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13232

East Asian (EAS) AF: 0.00 AC: 0 AN: 28270

South Asian (SAS) AF: 0.00 AC: 0 AN: 31072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2164

European-Non Finnish (NFE) AF: 0.00000456 AC: 2 AN: 438948

Other (OTH) AF: 0.00 AC: 0 AN: 29618

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.84

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: rs116965992; hg19: chr7-92760431;