rs431825171

Positions:

• chr3-45833099-GGCTTT-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020347.4(LZTFL1):​c.402_406del​(p.Pro136ThrfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LZTFL1 NM_020347.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.31

Genes affected

LZTFL1 (HGNC:6741): (leucine zipper transcription factor like 1) This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. [provided by RefSeq, Aug 2020]

(HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-45833099-GGCTTT-G is Pathogenic according to our data. Variant chr3-45833099-GGCTTT-G is described in ClinVar as [Pathogenic]. Clinvar id is 39770.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-45833099-GGCTTT-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTFL1	NM_020347.4	c.402_406del	p.Pro136ThrfsTer5	frameshift_variant	5/10	ENST00000296135.11	NP_065080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTFL1	ENST00000296135.11	c.402_406del	p.Pro136ThrfsTer5	frameshift_variant	5/10	1	NM_020347.4	ENSP00000296135	P1
	ENST00000699185.1	n.3796+5701_3796+5705del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome 17 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2012

- -

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: rs431825171; hg19: chr3-45874591;