rs1393142880

Variant names:

• chrX-129465529-C-T
• rs1393142880
• NM_001282874.2:c.3021G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-129465529-C-T
• chrX-129465529-C-A

Variant summary

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

The NM_001282874.2(SMARCA1):​c.3021G>A​(p.Arg1007Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000742 in 1,078,538 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000074 (0 hom. 4 hem.)
• Consequence: SMARCA1 NM_001282874.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

SMARCA1 (HGNC:11097): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1) This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

SMARCA1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics
• X-linked intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-129465529-C-T is Benign according to our data. Variant chrX-129465529-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 4 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282874.2. 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
	SMARCA1	NM_001282874.2	MANE Select	c.3021G>A	p.Arg1007Arg	synonymous	Exon 23 of 25	NP_001269803.1	B7ZLQ5
	SMARCA1	NM_001282875.2		c.2985G>A	p.Arg995Arg	synonymous	Exon 22 of 24	NP_001269804.1	A0A0A0MRP6
	SMARCA1	NM_003069.5		c.3021G>A	p.Arg1007Arg	synonymous	Exon 23 of 25	NP_003060.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA1	ENST00000371121.5	TSL:1 MANE Select	c.3021G>A	p.Arg1007Arg	synonymous	Exon 23 of 25	ENSP00000360162.4	B7ZLQ5
	SMARCA1	ENST00000371123.5	TSL:1	c.2985G>A	p.Arg995Arg	synonymous	Exon 22 of 24	ENSP00000360164.2	A0A0A0MRP6
	SMARCA1	ENST00000371122.8	TSL:1	c.3021G>A	p.Arg1007Arg	synonymous	Exon 23 of 25	ENSP00000360163.4	P28370-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000577 AC: 1 AN: 173181 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000392

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 AF: 0.00000742 AC: 8 AN: 1078538 Hom.: 0 Cov.: 26 AF XY: 0.0000116 AC XY: 4 AN XY: 346024

African (AFR) AF: 0.00 AC: 0 AN: 25925

American (AMR) AF: 0.0000290 AC: 1 AN: 34457

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19100

East Asian (EAS) AF: 0.00 AC: 0 AN: 29945

South Asian (SAS) AF: 0.00 AC: 0 AN: 52412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3993

European-Non Finnish (NFE) AF: 0.00000726 AC: 6 AN: 826922

Other (OTH) AF: 0.0000220 AC: 1 AN: 45392

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	-0.42
CADD	Benign	8.3
DANN	Benign	0.63
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1393142880; hg19: chrX-128599506;