chr19-38080969-CAA-C

Variant names:

• chr19-38080969-CAA-C
• rs34741674
• NM_015073.3:c.-310-273_-310-272delAA

Variant summary

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

The NM_015073.3(SIPA1L3):​c.-310-273_-310-272delAA 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 0.00087 (0 hom., cov: 0)
• Consequence: SIPA1L3 NM_015073.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

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]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L3	NM_015073.3	c.-310-273_-310-272delAA		intron_variant	Intron 2 of 21	ENST00000222345.11	NP_055888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L3	ENST00000222345.11	c.-310-286_-310-285delAA		intron_variant	Intron 2 of 21	1	NM_015073.3	ENSP00000222345.4
SIPA1L3	ENST00000476317.2	n.416-286_416-285delAA		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.000843 AC: 99 AN: 117468 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000752

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.000224

Gnomad SAS AF: 0.000550

Gnomad FIN AF: 0.00187

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.000648

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

GnomAD4 genome AF: 0.000868 AC: 102 AN: 117512 Hom.: 0 Cov.: 0 AF XY: 0.000976 AC XY: 55 AN XY: 56348

African (AFR) AF: 0.000971 AC: 31 AN: 31922

American (AMR) AF: 0.000751 AC: 9 AN: 11984

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 4 AN: 2766

East Asian (EAS) AF: 0.000224 AC: 1 AN: 4462

South Asian (SAS) AF: 0.000552 AC: 2 AN: 3622

European-Finnish (FIN) AF: 0.00187 AC: 12 AN: 6406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.000779 AC: 42 AN: 53924

Other (OTH) AF: 0.000645 AC: 1 AN: 1550

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs34741674; hg19: chr19-38571609;