7-93101341-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017654.4(SAMD9):​c.4757T>C​(p.Ile1586Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SAMD9
NM_017654.4 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.49
Variant links:
Genes affected
SAMD9 (HGNC:1348): (sterile alpha motif domain containing 9) This gene encodes a sterile alpha motif domain-containing protein. The encoded protein localizes to the cytoplasm and may play a role in regulating cell proliferation and apoptosis. Mutations in this gene are the cause of normophosphatemic familial tumoral calcinosis. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SAMD9NM_017654.4 linkuse as main transcriptc.4757T>C p.Ile1586Thr missense_variant 3/3 ENST00000379958.3 NP_060124.2
SAMD9NM_001193307.2 linkuse as main transcriptc.4757T>C p.Ile1586Thr missense_variant 2/2 NP_001180236.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SAMD9ENST00000379958.3 linkuse as main transcriptc.4757T>C p.Ile1586Thr missense_variant 3/31 NM_017654.4 ENSP00000369292 P1
SAMD9ENST00000620985.4 linkuse as main transcriptc.4757T>C p.Ile1586Thr missense_variant 2/22 ENSP00000484636 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxJun 27, 2019Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.80
T;.
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.5
M;M
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.2
.;D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.67
MutPred
0.35
Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);
MVP
0.70
MPC
0.73
ClinPred
0.99
D
GERP RS
4.6
Varity_R
0.52
gMVP
0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92730654; API