chr12-56164389-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_001330288.2(SMARCC2):c.3575C>T(p.Pro1192Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
SMARCC2
NM_001330288.2 missense
NM_001330288.2 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 5.50
Genes affected
SMARCC2 (HGNC:11105): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCC2. . Gene score misZ 3.9085 (greater than the threshold 3.09). Trascript score misZ 4.8151 (greater than threshold 3.09). GenCC has associacion of gene with Coffin-Siris syndrome 8, Coffin-Siris syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.10352972).
BP6
Variant 12-56164389-G-A is Benign according to our data. Variant chr12-56164389-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2575626.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCC2 | NM_001330288.2 | c.3575C>T | p.Pro1192Leu | missense_variant | 28/29 | ENST00000550164.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCC2 | ENST00000550164.6 | c.3575C>T | p.Pro1192Leu | missense_variant | 28/29 | 5 | NM_001330288.2 | A2 | |
ENST00000553176.1 | n.213-1840C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000839 AC: 21AN: 250164Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135246
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GnomAD4 exome AF: 0.000142 AC: 207AN: 1461522Hom.: 0 Cov.: 32 AF XY: 0.000136 AC XY: 99AN XY: 727026
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GnomAD4 genome AF: 0.000230 AC: 35AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74490
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
SMARCC2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
0.80
.;P
Vest4
MVP
MPC
0.15
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at