19-38081727-GGCCACCGCCACC-G

Position:

• chr19-38081727-GGCCACCGCCACC-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015073.3(SIPA1L3):​c.181_192del​(p.Ala61_Thr64del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,602,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: SIPA1L3 NM_015073.3 inframe_deletion
• Clinical Significance: Likely 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-38081727-GGCCACCGCCACC-G is Benign according to our data. Variant chr19-38081727-GGCCACCGCCACC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1659558.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L3	NM_015073.3	c.181_192del	p.Ala61_Thr64del	inframe_deletion	3/22	ENST00000222345.11	NP_055888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L3	ENST00000222345.11	c.181_192del	p.Ala61_Thr64del	inframe_deletion	3/22	1	NM_015073.3	ENSP00000222345	P1

Frequencies

GnomAD3 genomes AF: 0.000993 AC: 151 AN: 152072 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000286 AC: 63 AN: 220134 Hom.: 0 AF XY: 0.000295 AC XY: 36 AN XY: 121972

Gnomad AFR exome AF: 0.00177

Gnomad AMR exome AF: 0.000246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000189

Gnomad SAS exome AF: 0.000271

Gnomad FIN exome AF: 0.000168

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000184

GnomAD4 exome AF: 0.000267 AC: 387 AN: 1450620 Hom.: 0 AF XY: 0.000273 AC XY: 197 AN XY: 721318

Gnomad4 AFR exome AF: 0.00297

Gnomad4 AMR exome AF: 0.000275

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000231

Gnomad4 SAS exome AF: 0.000257

Gnomad4 FIN exome AF: 0.0000406

Gnomad4 NFE exome AF: 0.000202

Gnomad4 OTH exome AF: 0.000301

GnomAD4 genome AF: 0.000999 AC: 152 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.000847 AC XY: 63 AN XY: 74418

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.0000367 Hom.: 2

Bravo AF: 0.00134

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 30, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs562186095; hg19: chr19-38572367;