Variant chr5-178254982-G-C 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_173465.4(COL23A1):c.927C>G(p.Ile309Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,540 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

COL23A1
NM_173465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.569

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11607212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL23A1	NM_173465.4 linkuse as main transcript	c.927C>G	p.Ile309Met	missense_variant	16/29	ENST00000390654.8	NP_775736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL23A1	ENST00000390654.8 linkuse as main transcript	c.927C>G	p.Ile309Met	missense_variant	16/29	5	NM_173465.4	ENSP00000375069	P1	Q86Y22-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000561

AC:

AN:

249454

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000779

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:

0.00000616

AC:

AN:

1461496

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000496

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

May 24, 2024

The c.927C>G (p.I309M) alteration is located in exon 16 (coding exon 16) of the COL23A1 gene. This alteration results from a C to G substitution at nucleotide position 927, causing the isoleucine (I) at amino acid position 309 to be replaced by a methionine (M). 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

0.33

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0055

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.12

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.89

N;.

REVEL

Uncertain

0.48

Sift

Benign

0.061

T;.

Sift4G

Benign

0.11

T;T

Polyphen

0.055

B;.

Vest4

0.69

MutPred

0.23

Gain of phosphorylation at T306 (P = 0.1521);.;

MVP

0.79

MPC

0.58

ClinPred

0.085

GERP RS

-3.3

Varity_R

0.20

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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