chr9-26995828-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022901.3(LRRC19):c.806G>T(p.Ser269Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,451,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
LRRC19
NM_022901.3 missense
NM_022901.3 missense
Scores
1
11
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.96
Genes affected
LRRC19 (HGNC:23379): (leucine rich repeat containing 19) Predicted to enable signaling receptor activity. Acts upstream of or within positive regulation of NIK/NF-kappaB signaling. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
IFT74 (HGNC:21424): (intraflagellar transport 74) This gene encodes a core intraflagellar transport (IFT) protein which belongs to a multi-protein complex involved in the transport of ciliary proteins along axonemal microtubules. IFT proteins are found at the base of the cilium as well as inside the cilium, where they assemble into long arrays between the ciliary base and tip. This protein, together with intraflagellar transport protein 81, binds and transports tubulin within cilia and is required for ciliogenesis. Naturally occurring mutations in this gene are associated with amyotrophic lateral sclerosis--frontotemporal dementia and Bardet-Biedl Syndrome. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC19 | NM_022901.3 | c.806G>T | p.Ser269Ile | missense_variant | 5/5 | ENST00000380055.6 | |
IFT74 | NM_025103.4 | c.587+5633C>A | intron_variant | ENST00000380062.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC19 | ENST00000380055.6 | c.806G>T | p.Ser269Ile | missense_variant | 5/5 | 1 | NM_022901.3 | P1 | |
IFT74 | ENST00000380062.10 | c.587+5633C>A | intron_variant | 1 | NM_025103.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000326 AC: 8AN: 245344Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132552
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GnomAD4 exome AF: 0.0000145 AC: 21AN: 1451124Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8AN XY: 720392
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0053);
MVP
MPC
ClinPred
T
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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