Genetic Variant NM_173465.4:c.119G>T (chr5-178590079-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_173465.4(COL23A1):c.119G>T(p.Cys40Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,314,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

COL23A1
NM_173465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.175

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31267145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL23A1	NM_173465.4 link	c.119G>T	p.Cys40Phe	missense_variant	Exon 1 of 29	ENST00000390654.8	NP_775736.2	Q86Y22-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL23A1	ENST00000390654.8 link	c.119G>T	p.Cys40Phe	missense_variant	Exon 1 of 29	5	NM_173465.4	ENSP00000375069.3		Q86Y22-1

Frequencies

GnomAD3 genomes

AF:

0.0000530

AC:

AN:

150842

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000161

AC:

AN:

55984

AF XY:

0.000208

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000300

AC:

349

AN:

1163568

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

165

AN XY:

568372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23500

American (AMR)

AF:

0.00

AC:

AN:

17498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18250

East Asian (EAS)

AF:

0.00

AC:

AN:

24004

South Asian (SAS)

AF:

0.000352

AC:

AN:

45468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25310

Middle Eastern (MID)

AF:

0.000314

AC:

AN:

3180

European-Non Finnish (NFE)

AF:

0.000342

AC:

329

AN:

960618

Other (OTH)

AF:

0.0000656

AC:

AN:

45740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000530

AC:

AN:

150842

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41308

American (AMR)

AF:

0.00

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67584

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.119G>T (p.C40F) alteration is located in exon 1 (coding exon 1) of the COL23A1 gene. This alteration results from a G to T substitution at nucleotide position 119, causing the cysteine (C) at amino acid position 40 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0052

Eigen

Benign

0.073

Eigen_PC

Benign

0.090

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

0.81

PhyloP100

0.17

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

REVEL

Pathogenic

0.65

Sift

Uncertain

0.010

Sift4G

Benign

0.072

Polyphen

0.86

Vest4

0.42

MutPred

0.38

Loss of catalytic residue at L41 (P = 0.0139);

MVP

0.86

MPC

0.20

ClinPred

0.075

GERP RS

3.7

PromoterAI

0.062

Neutral

(source)

Varity_R

0.36

gMVP

0.052

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over