19-17226712-C-T

Variant names:

• chr19-17226712-C-T
• rs761673169
• NM_024578.3:c.89C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024578.3(OCEL1):​c.89C>T​(p.Pro30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,356,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: OCEL1 NM_024578.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20974636).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024578.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCEL1	NM_024578.3	MANE Select	c.89C>T	p.Pro30Leu	missense	Exon 2 of 6	NP_078854.1	Q9H607

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCEL1	ENST00000215061.9	TSL:1 MANE Select	c.89C>T	p.Pro30Leu	missense	Exon 2 of 6	ENSP00000215061.3	Q9H607
	OCEL1	ENST00000597836.5	TSL:2	c.-80C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000470270.1	M0QZ36
	OCEL1	ENST00000928402.1		c.89C>T	p.Pro30Leu	missense	Exon 2 of 6	ENSP00000598461.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000959 AC: 13 AN: 1356064 Hom.: 0 Cov.: 31 AF XY: 0.0000105 AC XY: 7 AN XY: 668360

African (AFR) AF: 0.00 AC: 0 AN: 28534

American (AMR) AF: 0.00 AC: 0 AN: 29182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20936

East Asian (EAS) AF: 0.00 AC: 0 AN: 35920

South Asian (SAS) AF: 0.00 AC: 0 AN: 73806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.0000122 AC: 13 AN: 1069244

Other (OTH) AF: 0.00 AC: 0 AN: 55776

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.20		Loss of glycosylation at P30 (P = 0.0068)
MVP		0.57
MPC		0.82
ClinPred		0.65	D
GERP RS		3.1
PromoterAI		-0.00040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.11
gMVP		0.31
Mutation Taster		=95/5	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: rs761673169; hg19: chr19-17337521;