chr3-45828480-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_020347.4(LZTFL1):c.736G>A(p.Asp246Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0766 in 1,614,000 control chromosomes in the GnomAD database, including 5,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.069 ( 431 hom., cov: 32)
Exomes 𝑓: 0.077 ( 4660 hom. )
Consequence
LZTFL1
NM_020347.4 missense
NM_020347.4 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 4.52
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0027333498).
BP6
?
Variant 3-45828480-C-T is Benign according to our data. Variant chr3-45828480-C-T is described in ClinVar as [Benign]. Clinvar id is 1164870.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTFL1 | NM_020347.4 | c.736G>A | p.Asp246Asn | missense_variant | 8/10 | ENST00000296135.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTFL1 | ENST00000296135.11 | c.736G>A | p.Asp246Asn | missense_variant | 8/10 | 1 | NM_020347.4 | P1 | |
ENST00000699185.1 | n.3796+1080C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0689 AC: 10481AN: 152138Hom.: 431 Cov.: 32
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GnomAD3 exomes AF: 0.0737 AC: 18532AN: 251412Hom.: 786 AF XY: 0.0758 AC XY: 10305AN XY: 135880
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GnomAD4 exome AF: 0.0774 AC: 113181AN: 1461744Hom.: 4660 Cov.: 32 AF XY: 0.0777 AC XY: 56509AN XY: 727192
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GnomAD4 genome ? AF: 0.0688 AC: 10481AN: 152256Hom.: 431 Cov.: 32 AF XY: 0.0706 AC XY: 5252AN XY: 74442
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8948
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MPC
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at