5-178247778-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_173465.4(COL23A1):c.1266G>A(p.Pro422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,613,324 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (25 hom.)
• Consequence: COL23A1 NM_173465.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.167

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-178247778-C-T is Benign according to our data. Variant chr5-178247778-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.167 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL23A1	NM_173465.4	c.1266G>A	p.Pro422=	synonymous_variant	21/29	ENST00000390654.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL23A1	ENST00000390654.8	c.1266G>A	p.Pro422=	synonymous_variant	21/29	5	NM_173465.4	P1

Frequencies

GnomAD3 genomes AF: 0.00291 AC: 443 AN: 152088 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00475

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00311 AC: 772 AN: 248226 Hom.: 1 AF XY: 0.00322 AC XY: 434 AN XY: 134864

Gnomad AFR exome AF: 0.000916

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00206

Gnomad FIN exome AF: 0.000791

Gnomad NFE exome AF: 0.00517

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00409 AC: 5973 AN: 1461118 Hom.: 25 Cov.: 32 AF XY: 0.00407 AC XY: 2956 AN XY: 726880

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00237

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.000974

Gnomad4 NFE exome AF: 0.00479

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.00291 AC: 443 AN: 152206 Hom.: 3 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74424

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00475

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00333 Hom.: 1

Bravo AF: 0.00284

EpiCase AF: 0.00578

EpiControl AF: 0.00676

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

COL23A1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	7.2
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs78984764; hg19: chr5-177674779;