7-93131118-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152703.5(SAMD9L):​c.*99C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 751,370 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (38 hom., cov: 32)
  • Exomes 𝑓: 0.015 (161 hom.)
• Consequence: SAMD9L NM_152703.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-93131118-G-A is Benign according to our data. Variant chr7-93131118-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1216669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

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>T		3_prime_UTR	Exon 5 of 5	NP_689916.2
	SAMD9L	NM_001303496.3		c.*99C>T		3_prime_UTR	Exon 5 of 5	NP_001290425.1	Q8IVG5-1
	SAMD9L	NM_001303497.3		c.*99C>T		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>T		3_prime_UTR	Exon 5 of 5	ENSP00000326247.4	Q8IVG5-1
	SAMD9L	ENST00000437805.5	TSL:1	c.*99C>T		3_prime_UTR	Exon 6 of 6	ENSP00000408796.1	Q8IVG5-1
	SAMD9L	ENST00000411955.5	TSL:5	c.*99C>T		3_prime_UTR	Exon 6 of 6	ENSP00000405760.1	Q8IVG5-1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2749 AN: 152036 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0796

Gnomad SAS AF: 0.00788

Gnomad FIN AF: 0.00812

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.0149 AC: 8958 AN: 599214 Hom.: 161 Cov.: 8 AF XY: 0.0148 AC XY: 4489 AN XY: 303690

African (AFR) AF: 0.0273 AC: 369 AN: 13522

American (AMR) AF: 0.00957 AC: 129 AN: 13480

Ashkenazi Jewish (ASJ) AF: 0.0137 AC: 181 AN: 13232

East Asian (EAS) AF: 0.0889 AC: 2513 AN: 28260

South Asian (SAS) AF: 0.00946 AC: 294 AN: 31062

European-Finnish (FIN) AF: 0.00876 AC: 254 AN: 28996

Middle Eastern (MID) AF: 0.00739 AC: 16 AN: 2164

European-Non Finnish (NFE) AF: 0.0109 AC: 4762 AN: 438884

Other (OTH) AF: 0.0149 AC: 440 AN: 29614

GnomAD4 genome AF: 0.0181 AC: 2755 AN: 152156 Hom.: 38 Cov.: 32 AF XY: 0.0179 AC XY: 1335 AN XY: 74400

African (AFR) AF: 0.0283 AC: 1176 AN: 41506

American (AMR) AF: 0.0134 AC: 204 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.0791 AC: 409 AN: 5168

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4818

European-Finnish (FIN) AF: 0.00812 AC: 86 AN: 10592

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 745 AN: 68004

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.00262 Hom.: 1

Bravo AF: 0.0196

Asia WGS AF: 0.0380 AC: 132 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;