19-17228303-G-C

Variant names:

• chr19-17228303-G-C
• rs14129
• NM_024578.3:c.666G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024578.3(OCEL1):​c.666G>C​(p.Lys222Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OCEL1 NM_024578.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746
• Publications: 19 publications found

Genes affected

OCEL1 (HGNC:26221): (occludin/ELL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

OCEL1 Gene-Disease associations (from GenCC):

• Aicardi syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCEL1	NM_024578.3	c.666G>C	p.Lys222Asn	missense_variant	Exon 5 of 6	ENST00000215061.9	NP_078854.1
OCEL1	XM_006722899.5	c.666G>C	p.Lys222Asn	missense_variant	Exon 5 of 6		XP_006722962.1
OCEL1	XM_047439441.1	c.*46G>C		3_prime_UTR_variant	Exon 4 of 4		XP_047295397.1
OCEL1	XM_047439442.1	c.*2G>C		3_prime_UTR_variant	Exon 4 of 4		XP_047295398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCEL1	ENST00000215061.9	c.666G>C	p.Lys222Asn	missense_variant	Exon 5 of 6	1	NM_024578.3	ENSP00000215061.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 5414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M;.;.
PhyloP100		0.75
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D;.;.
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.63
ClinPred		0.99	D
GERP RS		0.87
PromoterAI		0.011	Neutral
Varity_R		0.67
gMVP		0.51
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs14129; hg19: chr19-17339112;