22-23833701-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003073.5(SMARCB1):​c.1116G>C​(p.Thr372Thr) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

SMARCB1
NM_003073.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00007013
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.99
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP7
Synonymous conserved (PhyloP=-1.99 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCB1NM_003073.5 linkc.1116G>C p.Thr372Thr splice_region_variant, synonymous_variant Exon 8 of 9 ENST00000644036.2 NP_003064.2 Q12824-1
SMARCB1NM_001362877.2 linkc.1170G>C p.Thr390Thr splice_region_variant, synonymous_variant Exon 8 of 9 NP_001349806.1
SMARCB1NM_001317946.2 linkc.1143G>C p.Thr381Thr splice_region_variant, synonymous_variant Exon 8 of 9 NP_001304875.1 G5E975Q9H836
SMARCB1NM_001007468.3 linkc.1089G>C p.Thr363Thr splice_region_variant, synonymous_variant Exon 8 of 9 NP_001007469.1 Q12824-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCB1ENST00000644036.2 linkc.1116G>C p.Thr372Thr splice_region_variant, synonymous_variant Exon 8 of 9 NM_003073.5 ENSP00000494049.2 Q12824-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.40
DANN
Benign
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000070
dbscSNV1_RF
Benign
0.0020
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: chr22-24175888; API