GeneBe

rs62637011

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_014336.5(AIPL1):ā€‹c.617T>Cā€‹(p.Ile206Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

AIPL1
NM_014336.5 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.98
Variant links:
Genes affected
AIPL1 (HGNC:359): (aryl hydrocarbon receptor interacting protein like 1) Leber congenital amaurosis (LCA) is the most severe inherited retinopathy with the earliest age of onset and accounts for at least 5% of all inherited retinal diseases. Affected individuals are diagnosed at birth or in the first few months of life with nystagmus, severely impaired vision or blindness and an abnormal or flat electroretinogram. The photoreceptor/pineal-expressed gene, AIPL1, encoding aryl-hydrocarbon interacting protein-like 1, is located within the LCA4 candidate region. The encoded protein contains three tetratricopeptide motifs, consistent with chaperone or nuclear transport activity. Mutations in this gene may cause approximately 20% of recessive LCA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a mutagenesis_site No significant effect on interaction with NUB1. (size 0) in uniprot entity AIPL1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3566758).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AIPL1NM_014336.5 linkc.617T>C p.Ile206Thr missense_variant Exon 4 of 6 ENST00000381129.8 NP_055151.3 Q9NZN9-1F1T0B6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AIPL1ENST00000381129.8 linkc.617T>C p.Ile206Thr missense_variant Exon 4 of 6 1 NM_014336.5 ENSP00000370521.3 Q9NZN9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461874
Hom.:
0
Cov.:
37
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Uncertain
0.074
D
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.072
T;.;T;.;.;.;.;T;T
Eigen
Benign
0.065
Eigen_PC
Benign
0.18
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
D;D;D;T;D;D;D;D;D
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.36
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.3
L;.;.;.;.;L;.;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.0
N;N;.;.;.;.;.;.;.
REVEL
Benign
0.21
Sift
Benign
0.61
T;T;.;.;.;.;.;.;.
Sift4G
Benign
0.13
T;T;T;T;T;T;T;T;.
Polyphen
0.74
P;P;.;B;.;.;P;.;.
Vest4
0.50
MutPred
0.49
Gain of loop (P = 0.0435);.;.;Gain of loop (P = 0.0435);.;Gain of loop (P = 0.0435);.;.;.;
MVP
0.91
MPC
0.38
ClinPred
0.87
D
GERP RS
5.0
Varity_R
0.43
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-6330226; API