rs1060503018

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_003073.5(SMARCB1):​c.366A>C​(p.Glu122Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SMARCB1
NM_003073.5 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17
Variant links:
Genes affected
SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

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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;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCB1. . Gene score misZ 3.6016 (greater than the threshold 3.09). Trascript score misZ 4.8554 (greater than threshold 3.09). GenCC has associacion of gene with schwannomatosis 1, familial multiple meningioma, rhabdoid tumor predisposition syndrome 1, complex neurodevelopmental disorder, intellectual disability, autosomal dominant 15, familial rhabdoid tumor, schwannomatosis, Coffin-Siris syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.32441372).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMARCB1NM_003073.5 linkuse as main transcriptc.366A>C p.Glu122Asp missense_variant 4/9 ENST00000644036.2
SMARCB1NM_001362877.2 linkuse as main transcriptc.366A>C p.Glu122Asp missense_variant 4/9
SMARCB1NM_001317946.2 linkuse as main transcriptc.339A>C p.Glu113Asp missense_variant 4/9
SMARCB1NM_001007468.3 linkuse as main transcriptc.339A>C p.Glu113Asp missense_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMARCB1ENST00000644036.2 linkuse as main transcriptc.366A>C p.Glu122Asp missense_variant 4/9 NM_003073.5 A1Q12824-1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
.;T;T;T
Eigen
Benign
-0.022
Eigen_PC
Benign
-0.0094
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.95
.;.;.;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Uncertain
0.42
D
MutationAssessor
Benign
0.65
.;N;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.69
N;.;N;N
REVEL
Uncertain
0.48
Sift
Benign
0.19
T;.;T;T
Sift4G
Benign
0.28
T;.;T;T
Polyphen
0.0060, 0.011, 0.98
.;B;B;D
Vest4
0.62
MutPred
0.14
Loss of helix (P = 0.0626);.;Loss of helix (P = 0.0626);.;
MVP
0.84
ClinPred
0.62
D
GERP RS
1.6
Varity_R
0.13
gMVP
0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24143134; API