Variant 1-186383149-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017847.6(ODR4):c.227C>G(p.Ala76Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000033 in 1,543,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ODR4
NM_017847.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

Variant links:

Genes affected

ODR4 (HGNC:24299): (odr-4 GPCR localization factor homolog) Predicted to be involved in protein localization. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ODR4 links:

ODR4 (HGNC:):

ODR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ODR4	NM_017847.6 linkuse as main transcript	c.227C>G	p.Ala76Gly	missense_variant	3/14	ENST00000287859.11	NP_060317.3	Q5SWX8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ODR4	ENST00000287859.11 linkuse as main transcript	c.227C>G	p.Ala76Gly	missense_variant	3/14	1	NM_017847.6	ENSP00000287859.6	Q5SWX8-1
ODR4	ENST00000367470.8 linkuse as main transcript	c.227C>G	p.Ala76Gly	missense_variant	3/13	5		ENSP00000356440.3	Q5SWX8-2
ODR4	ENST00000419367.8 linkuse as main transcript	c.227C>G	p.Ala76Gly	missense_variant	3/13	2		ENSP00000395084.3	Q5SWX8-4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000120

AC:

AN:

149854

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

78624

show subpopulations

Gnomad AFR exome

AF:

0.000121

Gnomad AMR exome

AF:

0.000592

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000501

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1391666

Hom.:

Cov.:

AF XY:

0.0000423

AC XY:

AN XY:

686234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.000516

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:

0.0000176

Gnomad4 OTH exome

AF:

0.000173

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000554

AC:

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 30, 2021

The c.227C>G (p.A76G) alteration is located in exon 3 (coding exon 2) of the C1orf27 gene. This alteration results from a C to G substitution at nucleotide position 227, causing the alanine (A) at amino acid position 76 to be replaced by a glycine (G). 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

0.18

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;T

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.8

M;M;M

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.73

MVP

0.54

MPC

0.59

ClinPred

0.78

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.79

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over