7-93131118-G-A

Position:

• chr7-93131118-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMD9L	NM_152703.5	c.*99C>T		3_prime_UTR_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.*99C>T		3_prime_UTR_variant	5/5	1	NM_152703.5	ENSP00000326247	P1
SAMD9L	ENST00000437805.5	c.*99C>T		3_prime_UTR_variant	6/6	1		ENSP00000408796	P1
SAMD9L	ENST00000411955.5	c.*99C>T		3_prime_UTR_variant	6/6	5		ENSP00000405760	P1

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

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00957

Gnomad4 ASJ exome AF: 0.0137

Gnomad4 EAS exome AF: 0.0889

Gnomad4 SAS exome AF: 0.00946

Gnomad4 FIN exome AF: 0.00876

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.0149

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

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.0791

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.00812

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00262 Hom.: 1

Bravo AF: 0.0196

Asia WGS AF: 0.0380 AC: 132 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs116965992; hg19: chr7-92760431;