Variant 5-178256354-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173465.4(COL23A1):c.881G>A(p.Arg294Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000197 in 1,602,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

COL23A1
NM_173465.4 missense, splice_region

Scores

Splicing: ADA: 0.9498

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

COL23A1 (HGNC:22990): (collagen type XXIII alpha 1 chain) COL23A1 is a member of the transmembrane collagens, a subfamily of the nonfibrillar collagens that contain a single pass hydrophobic transmembrane domain (Banyard et al., 2003 [PubMed 12644459]).[supplied by OMIM, Mar 2008]

COL23A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31119883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL23A1	NM_173465.4 linkuse as main transcript	c.881G>A	p.Arg294Gln	missense_variant, splice_region_variant	15/29	ENST00000390654.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL23A1	ENST00000390654.8 linkuse as main transcript	c.881G>A	p.Arg294Gln	missense_variant, splice_region_variant	15/29	5	NM_173465.4	P1	Q86Y22-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000666

AC:

AN:

240404

Hom.:

AF XY:

0.0000761

AC XY:

AN XY:

131486

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000491

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.000207

AC:

300

AN:

1450368

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

148

AN XY:

721150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000245

Gnomad4 OTH exome

AF:

0.000403

GnomAD4 genome

AF:

0.000105

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000291

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000255

AC:

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.0000746

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

Dec 13, 2023

The c.881G>A (p.R294Q) alteration is located in exon 15 (coding exon 15) of the COL23A1 gene. This alteration results from a G to A substitution at nucleotide position 881, causing the arginine (R) at amino acid position 294 to be replaced by a glutamine (Q). 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

0.081

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.15

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

0.012

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

0.36

N;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.084

Sift

Benign

0.35

T;.

Sift4G

Benign

0.60

T;T

Polyphen

0.64

P;.

Vest4

0.45

MVP

0.89

MPC

0.32

ClinPred

0.16

GERP RS

4.4

Varity_R

0.095

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.60

SpliceAI score (max)

0.12

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