rs62637011

Positions:

• chr17-6426906-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The ENST00000381129.8(AIPL1):​c.617T>A​(p.Ile206Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I206V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AIPL1 ENST00000381129.8 missense
• Clinical Significance: not provided no classification provided O:2
• Conservation: PhyloP100: 4.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIPL1	NM_014336.5	c.617T>A	p.Ile206Asn	missense_variant	4/6	ENST00000381129.8	NP_055151.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIPL1	ENST00000381129.8	c.617T>A	p.Ile206Asn	missense_variant	4/6	1	NM_014336.5	ENSP00000370521	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:2

Revision: no classification provided

Submissions by phenotype

Leber congenital amaurosis 4 Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

not provided Other:1

not provided, no classification provided

literature only

Retina International

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;T;.;.;.;.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.6	L;.;.;.;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.8	N;N;.;.;.;.;.;.;.
REVEL	Uncertain	0.40
Sift	Benign	0.51	T;T;.;.;.;.;.;.;.
Sift4G	Uncertain	0.048	D;T;D;T;D;D;D;T;.
Polyphen		0.95	P;D;.;P;.;.;D;.;.
Vest4		0.80
MutPred		0.75		Loss of helix (P = 0.0558);.;.;Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);.;.;.;
MVP		0.94
MPC		0.44
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.70
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs62637011; hg19: chr17-6330226;