Variant 22-23764377-A-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_182520.3(C22orf15):c.230A>G(p.Tyr77Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000624 in 1,554,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

C22orf15
NM_182520.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

C22orf15 (HGNC:15558): (chromosome 22 open reading frame 15)

C22orf15 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
C22orf15	NM_182520.3 linkuse as main transcript	c.230A>G	p.Tyr77Cys	missense_variant	3/6	ENST00000402217.8	NP_872326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C22orf15	ENST00000402217.8 linkuse as main transcript	c.230A>G	p.Tyr77Cys	missense_variant	3/6	2	NM_182520.3	ENSP00000384965	A2	Q8WYQ4-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000373

AC:

AN:

160678

Hom.:

AF XY:

0.0000235

AC XY:

AN XY:

85232

show subpopulations

Gnomad AFR exome

AF:

0.000726

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1401882

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

691800

show subpopulations

Gnomad4 AFR exome

AF:

0.00148

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:

0.0000172

GnomAD4 genome

AF:

0.000322

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000250

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.0000627

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

Oct 27, 2021

The c.230A>G (p.Y77C) alteration is located in exon 3 (coding exon 3) of the C22orf15 gene. This alteration results from a A to G substitution at nucleotide position 230, causing the tyrosine (Y) at amino acid position 77 to be replaced by a cysteine (C). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

L;.;L

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Pathogenic

-7.4

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.98

D;.;D

Vest4

0.69

MVP

0.37

MPC

0.63

ClinPred

0.25

GERP RS

2.5

Varity_R

0.44

gMVP

0.51

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