7-93135669-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152703.5(SAMD9L):c.303G>A(p.Gln101Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,613,698 control chromosomes in the GnomAD database, including 36,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 9123 hom., cov: 32)

Exomes 𝑓: 0.16 ( 26994 hom. )

Consequence

SAMD9L
NM_152703.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.48

Publications

18 publications found

Variant links:

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

SAMD9L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-93135669-C-T is Benign according to our data. Variant chr7-93135669-C-T is described in ClinVar as Benign. ClinVar VariationId is 1170232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD9L	NM_152703.5 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 5 of 5	ENST00000318238.9	NP_689916.2	Q8IVG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD9L	ENST00000318238.9 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 5 of 5	1	NM_152703.5	ENSP00000326247.4		Q8IVG5-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42345

AN:

151878

Hom.:

9090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.0874

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0949

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.238

GnomAD2 exomes

AF:

0.225

AC:

56455

AN:

250940

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.0829

Gnomad EAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.0991

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.158

AC:

230418

AN:

1461702

Hom.:

26994

Cov.:

AF XY:

0.153

AC XY:

111495

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.570

AC:

19072

AN:

33468

American (AMR)

AF:

0.416

AC:

18615

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0826

AC:

2158

AN:

26132

East Asian (EAS)

AF:

0.547

AC:

21688

AN:

39682

South Asian (SAS)

AF:

0.125

AC:

10756

AN:

86252

European-Finnish (FIN)

AF:

0.103

AC:

5478

AN:

53400

Middle Eastern (MID)

AF:

0.0851

AC:

491

AN:

5768

European-Non Finnish (NFE)

AF:

0.127

AC:

141344

AN:

1111908

Other (OTH)

AF:

0.179

AC:

10816

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10200

20400

30599

40799

50999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5712

11424

17136

22848

28560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.279

AC:

42444

AN:

151996

Hom.:

9123

Cov.:

AF XY:

0.278

AC XY:

20625

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.567

AC:

23473

AN:

41432

American (AMR)

AF:

0.333

AC:

5074

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

303

AN:

3468

East Asian (EAS)

AF:

0.568

AC:

2939

AN:

5176

South Asian (SAS)

AF:

0.130

AC:

625

AN:

4822

European-Finnish (FIN)

AF:

0.0949

AC:

1003

AN:

10564

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8385

AN:

67966

Other (OTH)

AF:

0.244

AC:

515

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1273

2547

3820

5094

6367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.193

Hom.:

11385

Bravo

AF:

0.313

Asia WGS

AF:

0.359

AC:

1247

AN:

3476

EpiCase

AF:

0.125

EpiControl

AF:

0.119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 06, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SAMD9L-related disorder

Benign:1

Feb 09, 2023

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.28

(source)

DANN

Benign

0.30

PhyloP100

-1.5

PromoterAI

-0.0049

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over