19-17227000-G-A

Position:

• chr19-17227000-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024578.3(OCEL1):​c.253G>A​(p.Gly85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000063 in 1,428,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: OCEL1 NM_024578.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.499

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034835875).
• BP6: Variant 19-17227000-G-A is Benign according to our data. Variant chr19-17227000-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2407591.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCEL1	NM_024578.3	c.253G>A	p.Gly85Arg	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.253G>A	p.Gly85Arg	missense_variant	3/6	1	NM_024578.3	ENSP00000215061.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000630 AC: 9 AN: 1428540 Hom.: 0 Cov.: 34 AF XY: 0.00000985 AC XY: 7 AN XY: 710612

Gnomad4 AFR exome AF: 0.000195

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: 9.08e-7

Gnomad4 OTH exome AF: 0.0000339

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.6
DANN	Benign	0.84
DEOGEN2	Benign	0.000095	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.035	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.90	N;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.080	N;.;.
REVEL	Benign	0.013
Sift	Benign	0.59	T;.;.
Sift4G	Benign	0.59	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.089
MutPred		0.22		Gain of MoRF binding (P = 0.0113);Gain of MoRF binding (P = 0.0113);.;
MVP		0.22
MPC		0.25
ClinPred		0.048	T
GERP RS		0.51
Varity_R		0.035
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs765147948; hg19: chr19-17337809;