19-38080969-CAAA-CAA

Variant names:

• chr19-38080969-CA-C
• rs34741674
• NM_015073.3:c.-310-272delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015073.3(SIPA1L3):​c.-310-272delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (7636 hom., cov: 0)
• Consequence: SIPA1L3 NM_015073.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-38080969-CA-C is Benign according to our data. Variant chr19-38080969-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1244101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

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.-310-272delA		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.-310-286delA		intron	N/A	ENSP00000222345.4	O60292
	SIPA1L3	ENST00000911499.1		c.-310-286delA		intron	N/A	ENSP00000581558.1
	SIPA1L3	ENST00000911500.1		c.-310-286delA		intron	N/A	ENSP00000581559.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 47123 AN: 117238 Hom.: 7646 Cov.: 0

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.402 AC: 47129 AN: 117280 Hom.: 7636 Cov.: 0 AF XY: 0.402 AC XY: 22607 AN XY: 56252

African (AFR) AF: 0.445 AC: 14173 AN: 31864

American (AMR) AF: 0.489 AC: 5846 AN: 11964

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 807 AN: 2766

East Asian (EAS) AF: 0.632 AC: 2816 AN: 4458

South Asian (SAS) AF: 0.323 AC: 1170 AN: 3620

European-Finnish (FIN) AF: 0.313 AC: 2007 AN: 6412

Middle Eastern (MID) AF: 0.325 AC: 63 AN: 194

European-Non Finnish (NFE) AF: 0.361 AC: 19427 AN: 53770

Other (OTH) AF: 0.365 AC: 565 AN: 1550

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs34741674; hg19: chr19-38571609;