Variant 19-38081727-GGCCACC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_015073.3(SIPA1L3):c.187_192del(p.Ala63_Thr64del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,602,790 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

SIPA1L3
NM_015073.3 inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.25

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 19-38081727-GGCCACC-G is Benign according to our data. Variant chr19-38081727-GGCCACC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2054669.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}. Variant chr19-38081727-GGCCACC-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1L3	NM_015073.3 linkuse as main transcript	c.187_192del	p.Ala63_Thr64del	inframe_deletion	3/22	ENST00000222345.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIPA1L3	ENST00000222345.11 linkuse as main transcript	c.187_192del	p.Ala63_Thr64del	inframe_deletion	3/22	1	NM_015073.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

313

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00115

AC:

254

AN:

220134

Hom.:

AF XY:

0.00100

AC XY:

122

AN XY:

121972

show subpopulations

Gnomad AFR exome

AF:

0.00378

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00202

Gnomad SAS exome

AF:

0.000406

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.000590

Gnomad OTH exome

AF:

0.000551

GnomAD4 exome

AF:

0.00102

AC:

1480

AN:

1450600

Hom.:

AF XY:

0.000934

AC XY:

674

AN XY:

721312

show subpopulations

Gnomad4 AFR exome

AF:

0.00501

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.00113

Gnomad4 SAS exome

AF:

0.000583

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.000870

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152190

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00443

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00175

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.00331

Bravo

AF:

0.00212

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	SIPA1L3: PM4, BS1:Supporting -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Oct 22, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over