NM_001330288.2:c.3592G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001330288.2(SMARCC2):​c.3592G>A​(p.Ala1198Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,404 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SMARCC2
NM_001330288.2 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67
Variant links:
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.

BP4
Computational evidence support a benign effect (MetaRNN=0.20585695).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCC2NM_001330288.2 linkc.3592G>A p.Ala1198Thr missense_variant Exon 28 of 29 ENST00000550164.6 NP_001317217.1 Q8TAQ2F8VXC8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCC2ENST00000550164.6 linkc.3592G>A p.Ala1198Thr missense_variant Exon 28 of 29 5 NM_001330288.2 ENSP00000449396.1 F8VXC8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
248782
Hom.:
0
AF XY:
0.0000371
AC XY:
5
AN XY:
134746
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461404
Hom.:
0
Cov.:
32
AF XY:
0.0000124
AC XY:
9
AN XY:
726974
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

Coffin-Siris syndrome 8 Uncertain:1
Sep 26, 2021
New York Genome Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0075
T;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Benign
0.66
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.31
N;N
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.15
T;T
Polyphen
1.0
.;D
Vest4
0.42
MutPred
0.21
.;Gain of glycosylation at A1167 (P = 0.0714);
MVP
0.21
MPC
0.15
ClinPred
0.34
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs772189962; hg19: chr12-56558156; API