5-178257552-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173465.4(COL23A1):c.745C>T(p.Pro249Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL23A1 NM_173465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04

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 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=0.26789853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL23A1	NM_173465.4	c.745C>T	p.Pro249Ser	missense_variant	13/29	ENST00000390654.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL23A1	ENST00000390654.8	c.745C>T	p.Pro249Ser	missense_variant	13/29	5	NM_173465.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1409856 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 696414

Gnomad4 AFR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.745C>T (p.P249S) alteration is located in exon 13 (coding exon 13) of the COL23A1 gene. This alteration results from a C to T substitution at nucleotide position 745, causing the proline (P) at amino acid position 249 to be replaced by a serine (S). 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	0.071
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	0.97	D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.091
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.031	D;T
Polyphen		0.43	B;.
Vest4		0.25
MutPred		0.39		Gain of phosphorylation at P249 (P = 0.0028);.;
MVP		0.93
MPC		0.35
ClinPred		0.61	D
GERP RS		3.5
Varity_R		0.060
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-177684553;