chr19-38080969-C-CAAAA

Variant names:

• chr19-38080969-C-CAAAA
• rs34741674
• NM_015073.3:c.-310-275_-310-272dupAAAA

Variant summary

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

The NM_015073.3(SIPA1L3):​c.-310-275_-310-272dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00014 (0 hom., cov: 0)
• Consequence: SIPA1L3 NM_015073.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

Genes affected

SIPA1L3 (HGNC:23801): (signal induced proliferation associated 1 like 3) This gene belongs to the signal induced proliferation associated 1 family of genes, which encode GTPase-activating proteins specific for the GTP-binding protein Rap1. Rap1 has been implicated in regulation of cell adhesion, cell polarity, and organization of the cytoskeleton. Like other members of the family, the protein encoded by this gene contains RapGAP and PDZ domains. In addition, this protein contains a C-terminal leucine zipper domain. This gene is proposed to function in epithelial cell morphogenesis and establishment or maintenance of polarity. Consistently, expression of the protein in cell culture showed localization to cell-cell borders in apical regions, and downregulation of the gene in 3D Caco2 cell culture resulted in abnormal cell polarity and morphogenesis. Allelic variants of this gene have been associated with congenital cataracts in humans. [provided by RefSeq, Feb 2016]

SIPA1L3 Gene-Disease associations (from GenCC):

• cataract 45

  Inheritance: AD, AR, SD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015073.3. 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
	SIPA1L3	NM_015073.3	MANE Select	c.-310-275_-310-272dupAAAA		intron	N/A	NP_055888.1	O60292

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L3	ENST00000222345.11	TSL:1 MANE Select	c.-310-287_-310-286insAAAA		intron	N/A	ENSP00000222345.4	O60292
	SIPA1L3	ENST00000911499.1		c.-310-287_-310-286insAAAA		intron	N/A	ENSP00000581558.1
	SIPA1L3	ENST00000911500.1		c.-310-287_-310-286insAAAA		intron	N/A	ENSP00000581559.1

Frequencies

GnomAD3 genomes AF: 0.000128 AC: 15 AN: 117530 Hom.: 0 Cov.: 0

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: 0.00412

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000145 AC: 17 AN: 117574 Hom.: 0 Cov.: 0 AF XY: 0.000195 AC XY: 11 AN XY: 56378

African (AFR) AF: 0.00 AC: 0 AN: 31932

American (AMR) AF: 0.00 AC: 0 AN: 11990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2768

East Asian (EAS) AF: 0.00 AC: 0 AN: 4462

South Asian (SAS) AF: 0.00414 AC: 15 AN: 3622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53942

Other (OTH) AF: 0.00129 AC: 2 AN: 1552

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34741674; hg19: chr19-38571609;