chr19-38081088-A-G

Position:

• chr19-38081088-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015073.3(SIPA1L3):​c.-310-168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,066 control chromosomes in the GnomAD database, including 2,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2103 hom., cov: 32)
• Consequence: SIPA1L3 NM_015073.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-38081088-A-G is Benign according to our data. Variant chr19-38081088-A-G is described in ClinVar as [Benign]. Clinvar id is 1245591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1L3	NM_015073.3	c.-310-168A>G		intron_variant		ENST00000222345.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIPA1L3	ENST00000222345.11	c.-310-168A>G		intron_variant		1	NM_015073.3	P1
SIPA1L3	ENST00000476317.2	n.416-168A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24417 AN: 151948 Hom.: 2097 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.161 AC: 24466 AN: 152066 Hom.: 2103 Cov.: 32 AF XY: 0.161 AC XY: 11963 AN XY: 74310

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0841

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.168

Alfa AF: 0.155 Hom.: 244

Bravo AF: 0.164

Asia WGS AF: 0.148 AC: 514 AN: 3478

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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.68

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: rs1725512; hg19: chr19-38571728;