11-65644996-G-C

Variant names:

• chr11-65644996-G-C
• rs2306364
• NM_006747.4:c.1026G>C

Variant summary

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

The NM_006747.4(SIPA1):​c.1026G>C​(p.Ala342Ala) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIPA1 NM_006747.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.71
• Publications: 29 publications found

Genes affected

SIPA1 (HGNC:10885): (signal-induced proliferation-associated 1) The product of this gene is a mitogen induced GTPase activating protein (GAP). It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. This protein may also hamper mitogen-induced cell cycle progression when abnormally or prematurely expressed. It is localized to the perinuclear region. Two alternatively spliced variants encoding the same isoform have been characterized to date. [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=-0.76).
• BP7: Synonymous conserved (PhyloP=-7.71 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006747.4. 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
	SIPA1	NM_006747.4	MANE Select	c.1026G>C	p.Ala342Ala	synonymous	Exon 5 of 16	NP_006738.3
	SIPA1	NM_153253.30		c.1026G>C	p.Ala342Ala	synonymous	Exon 5 of 16	NP_694985.29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1	ENST00000534313.6	TSL:1 MANE Select	c.1026G>C	p.Ala342Ala	synonymous	Exon 5 of 16	ENSP00000436269.1	Q96FS4
	SIPA1	ENST00000394224.4	TSL:1	c.1026G>C	p.Ala342Ala	synonymous	Exon 5 of 16	ENSP00000377771.3
	SIPA1	ENST00000969242.1		c.1026G>C	p.Ala342Ala	synonymous	Exon 5 of 17	ENSP00000639301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251014 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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.091
DANN	Benign	0.78
PhyloP100		-7.7
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: rs2306364; hg19: chr11-65412467;