19-17227037-G-T

Position:

• chr19-17227037-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024578.3(OCEL1):​c.290G>T​(p.Arg97Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OCEL1 NM_024578.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.890

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 (HGNC:):

ACMG classification

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	Protein	UniProt
OCEL1	NM_024578.3	c.290G>T	p.Arg97Leu	missense_variant	3/6	ENST00000215061.9	NP_078854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCEL1	ENST00000215061.9	c.290G>T	p.Arg97Leu	missense_variant	3/6	1	NM_024578.3	ENSP00000215061.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451816 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 722448

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.290G>T (p.R97L) alteration is located in exon 3 (coding exon 3) of the OCEL1 gene. This alteration results from a G to T substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0051	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D;.;.
REVEL	Benign	0.028
Sift	Uncertain	0.012	D;.;.
Sift4G	Benign	0.18	T;T;T
Polyphen		0.031	B;.;.
Vest4		0.21
MutPred		0.18		Gain of ubiquitination at K92 (P = 0.0268);Gain of ubiquitination at K92 (P = 0.0268);.;
MVP		0.20
MPC		0.33
ClinPred		0.31	T
GERP RS		-3.3
Varity_R		0.11
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 14

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

Publications

LitVar

Other links and lift over

dbSNP: rs143732733; hg19: chr19-17337846;