12-56163728-C-G

Variant names:

• chr12-56163728-C-G
• rs181267165
• NM_001330288.2:c.3699G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001330288.2(SMARCC2):​c.3699G>C​(p.Pro1233Pro) variant causes a 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1233P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCC2 NM_001330288.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.68
• Publications: 3 publications found

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]

ENSG00000258199 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-4.68 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCC2	NM_001330288.2	MANE Select	c.3699G>C	p.Pro1233Pro	synonymous	Exon 29 of 29	NP_001317217.1	F8VXC8
	SMARCC2	NM_003075.5		c.3606G>C	p.Pro1202Pro	synonymous	Exon 28 of 28	NP_003066.2
	SMARCC2	NM_001130420.3		c.3420G>C	p.Pro1140Pro	synonymous	Exon 30 of 30	NP_001123892.1	Q8TAQ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCC2	ENST00000550164.6	TSL:5 MANE Select	c.3699G>C	p.Pro1233Pro	synonymous	Exon 29 of 29	ENSP00000449396.1	F8VXC8
	SMARCC2	ENST00000267064.8	TSL:1	c.3606G>C	p.Pro1202Pro	synonymous	Exon 28 of 28	ENSP00000267064.4	Q8TAQ2-1
	SMARCC2	ENST00000394023.7	TSL:1	c.3420G>C	p.Pro1140Pro	synonymous	Exon 30 of 30	ENSP00000377591.3	Q8TAQ2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 161938 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1355184 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 671012

African (AFR) AF: 0.00 AC: 0 AN: 26450

American (AMR) AF: 0.00 AC: 0 AN: 21390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22586

East Asian (EAS) AF: 0.00 AC: 0 AN: 32066

South Asian (SAS) AF: 0.00 AC: 0 AN: 70354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069632

Other (OTH) AF: 0.00 AC: 0 AN: 55770

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.47
DANN	Benign	0.65
PhyloP100		-4.7

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

Other links and lift over

dbSNP: rs181267165; hg19: chr12-56557512;