dbSNP rs1872217560: SMARCC2:p.Ala1232Thr (chr12-56163733-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330288.2(SMARCC2):c.3694G>A(p.Ala1232Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMARCC2
NM_001330288.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Publications

0 publications found

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]

SMARCC2 links:

ENSG00000258199 (HGNC:):

ENSG00000258199 links:

MYL6 (HGNC:7587): (myosin light chain 6) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain that is expressed in smooth muscle and non-muscle tissues. Genomic sequences representing several pseudogenes have been described and two transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11937833).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330288.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCC2	NM_001330288.2	MANE Select	c.3694G>A	p.Ala1232Thr	missense	Exon 29 of 29	NP_001317217.1	F8VXC8
SMARCC2	NM_003075.5		c.3601G>A	p.Ala1201Thr	missense	Exon 28 of 28	NP_003066.2
SMARCC2	NM_001130420.3		c.3415G>A	p.Ala1139Thr	missense	Exon 30 of 30	NP_001123892.1	Q8TAQ2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCC2	ENST00000550164.6	TSL:5 MANE Select	c.3694G>A	p.Ala1232Thr	missense	Exon 29 of 29	ENSP00000449396.1	F8VXC8
SMARCC2	ENST00000267064.8	TSL:1	c.3601G>A	p.Ala1201Thr	missense	Exon 28 of 28	ENSP00000267064.4	Q8TAQ2-1
SMARCC2	ENST00000394023.7	TSL:1	c.3415G>A	p.Ala1139Thr	missense	Exon 30 of 30	ENSP00000377591.3	Q8TAQ2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1359938

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673872

African (AFR)

AF:

0.00

AC:

AN:

26550

American (AMR)

AF:

0.00

AC:

AN:

21664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22738

East Asian (EAS)

AF:

0.00

AC:

AN:

32236

South Asian (SAS)

AF:

0.00

AC:

AN:

70884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5472

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072734

Other (OTH)

AF:

0.00

AC:

AN:

55958

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.20

Eigen_PC

Benign

0.0047

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.5

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.39

REVEL

Benign

0.11

Sift

Benign

0.034

Sift4G

Benign

0.47

Polyphen

0.0020

Vest4

0.22

MutPred

0.26

Gain of glycosylation at A1201 (P = 3e-04)

MVP

0.32

MPC

0.15

ClinPred

0.85

GERP RS

4.6

Varity_R

0.25

gMVP

0.12

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over