chr19-38080969-CA-C

Position:

• chr19-38080969-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015073.3(SIPA1L3):​c.-310-272del 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L3	NM_015073.3	c.-310-272del		intron_variant		ENST00000222345.11	NP_055888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L3	ENST00000222345.11	c.-310-272del		intron_variant		1	NM_015073.3	ENSP00000222345	P1
SIPA1L3	ENST00000476317.2	n.416-272del		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.365

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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;