NM_001330288.2:c.3513G>A

Variant names:

• chr12-56164451-C-T
• rs1227453567
• NM_001330288.2:c.3513G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001330288.2(SMARCC2):​c.3513G>A​(p.Ala1171Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,944 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SMARCC2 NM_001330288.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62
• Publications: 0 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]

SMARCC2 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Coffin-Siris syndrome 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ENSG00000258199 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 12-56164451-C-T is Benign according to our data. Variant chr12-56164451-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.62 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.3513G>A	p.Ala1171Ala	synonymous	Exon 28 of 29	NP_001317217.1	F8VXC8
	SMARCC2	NM_003075.5		c.3420G>A	p.Ala1140Ala	synonymous	Exon 27 of 28	NP_003066.2
	SMARCC2	NM_001130420.3		c.3317-83G>A		intron	N/A	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.3513G>A	p.Ala1171Ala	synonymous	Exon 28 of 29	ENSP00000449396.1	F8VXC8
	SMARCC2	ENST00000267064.8	TSL:1	c.3420G>A	p.Ala1140Ala	synonymous	Exon 27 of 28	ENSP00000267064.4	Q8TAQ2-1
	SMARCC2	ENST00000394023.7	TSL:1	c.3317-83G>A		intron	N/A	ENSP00000377591.3	Q8TAQ2-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251322 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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461824 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.0000658 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		1.6
BranchPoint Hunter		0.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs1227453567; hg19: chr12-56558235;