rs776375139

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM1PP3BS2

The NM_152703.5(SAMD9L):c.2963T>C(p.Ile988Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I988V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SAMD9L
NM_152703.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 4.19

Publications

0 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, 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

SAMD9L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 9 uncertain in NM_152703.5

PP3

MetaRNN computational evidence supports a deleterious effect, 0.787

BS2

High AC in GnomAdExome4 at 7 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD9L	NM_152703.5	MANE Select	c.2963T>C	p.Ile988Thr	missense	Exon 5 of 5	NP_689916.2
SAMD9L	NM_001303496.3		c.2963T>C	p.Ile988Thr	missense	Exon 5 of 5	NP_001290425.1	Q8IVG5-1
SAMD9L	NM_001303497.3		c.2963T>C	p.Ile988Thr	missense	Exon 6 of 6	NP_001290426.1	Q8IVG5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAMD9L	ENST00000318238.9	TSL:1 MANE Select	c.2963T>C	p.Ile988Thr	missense	Exon 5 of 5	ENSP00000326247.4	Q8IVG5-1
SAMD9L	ENST00000414791.6	TSL:1	c.2963T>C	p.Ile988Thr	missense	Exon 2 of 2	ENSP00000396137.2	Q8IVG5-1
SAMD9L	ENST00000437805.5	TSL:1	c.2963T>C	p.Ile988Thr	missense	Exon 6 of 6	ENSP00000408796.1	Q8IVG5-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

250436

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461010

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.000157

AC:

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111372

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.000131

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.6

PhyloP100

4.2

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.79

MutPred

0.63

Gain of catalytic residue at I988 (P = 0.015)

MVP

0.60

MPC

0.49

ClinPred

0.60

GERP RS

5.2

Varity_R

0.29

gMVP

0.34

Mutation Taster

=63/37

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over