22-23791855-G-C

Variant names:

• chr22-23791855-G-C
• NM_003073.5:c.193G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_003073.5(SMARCB1):​c.193G>C​(p.Ala65Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a region_of_interest DNA-binding (size 112) in uniprot entity SNF5_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_003073.5
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCB1	NM_003073.5	c.193G>C	p.Ala65Pro	missense_variant	Exon 2 of 9	ENST00000644036.2	NP_003064.2
SMARCB1	NM_001362877.2	c.193G>C	p.Ala65Pro	missense_variant	Exon 2 of 9		NP_001349806.1
SMARCB1	NM_001317946.2	c.193G>C	p.Ala65Pro	missense_variant	Exon 2 of 9		NP_001304875.1
SMARCB1	NM_001007468.3	c.193G>C	p.Ala65Pro	missense_variant	Exon 2 of 9		NP_001007469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2	c.193G>C	p.Ala65Pro	missense_variant	Exon 2 of 9		NM_003073.5	ENSP00000494049.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;T;T;.;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;.;.;.;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Benign	0.90	L;L;.;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N;.;N;N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.22	T;.;T;T;T;T
Sift4G	Benign	0.17	T;.;T;T;T;T
Polyphen		0.091, 0.15, 0.97	.;B;B;.;.;D
Vest4		0.39
MutPred		0.25		Gain of catalytic residue at A65 (P = 0.0596);Gain of catalytic residue at A65 (P = 0.0596);Gain of catalytic residue at A65 (P = 0.0596);Gain of catalytic residue at A65 (P = 0.0596);Gain of catalytic residue at A65 (P = 0.0596);Gain of catalytic residue at A65 (P = 0.0596);
MVP		0.82
MPC		1.7
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.72
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr22-24134042;