Variant 4-48857324-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017830.4(OCIAD1):c.659C>T(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OCIAD1
NM_017830.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

OCIAD1 (HGNC:16074): (OCIA domain containing 1) Predicted to be involved in several processes, including hematopoietic stem cell homeostasis; positive regulation of receptor signaling pathway via JAK-STAT; and regulation of stem cell differentiation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

OCIAD1 links:

OCIAD1-AS1 (HGNC:40751): (OCIAD1 antisense RNA 1)

OCIAD1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14821899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCIAD1	NM_017830.4 link	c.659C>T	p.Pro220Leu	missense_variant	8/9	ENST00000264312.12	NP_060300.1	Q9NX40-1A0A024R9U3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCIAD1	ENST00000264312.12 link	c.659C>T	p.Pro220Leu	missense_variant	8/9	1	NM_017830.4	ENSP00000264312.7		Q9NX40-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.674C>T (p.P225L) alteration is located in exon 8 (coding exon 8) of the OCIAD1 gene. This alteration results from a C to T substitution at nucleotide position 674, causing the proline (P) at amino acid position 225 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

0.076

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T;T;T;T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

D;.;.;D;.;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;N;.;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

N;N;N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.27

T;T;T;D;T;T

Sift4G

Benign

0.67

T;T;T;T;T;T

Polyphen

0.85

P;B;B;.;B;B

Vest4

0.31

MutPred

0.23

.;Gain of glycosylation at S221 (P = 0.0154);Gain of glycosylation at S221 (P = 0.0154);.;Gain of glycosylation at S221 (P = 0.0154);Gain of glycosylation at S221 (P = 0.0154);

MVP

0.50

MPC

0.14

ClinPred

0.68

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.083

gMVP

0.29

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over