5-178256868-T-G

Variant summary

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

The NM_173465.4(COL23A1):c.835A>C(p.Lys279Gln) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: COL23A1 NM_173465.4 missense, splice_region
• Scores: Splicing: ADA: 0.02102
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

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=0.4157403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL23A1	NM_173465.4	c.835A>C	p.Lys279Gln	missense_variant, splice_region_variant	14/29	ENST00000390654.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL23A1	ENST00000390654.8	c.835A>C	p.Lys279Gln	missense_variant, splice_region_variant	14/29	5	NM_173465.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Dec 04, 2023

The c.835A>C (p.K279Q) alteration is located in exon 14 (coding exon 14) of the COL23A1 gene. This alteration results from a A to C substitution at nucleotide position 835, causing the lysine (K) at amino acid position 279 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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.14
Sift	Uncertain	0.026	D;.
Sift4G	Benign	0.13	T;T
Polyphen		0.24	B;.
Vest4		0.55
MutPred		0.47		Loss of methylation at K279 (P = 0.0024);.;
MVP		0.42
MPC		0.27
ClinPred		0.84	D
GERP RS		4.8
Varity_R		0.32
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.021
dbscSNV1_RF	Benign	0.23
SpliceAI score (max)		0.040		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: chr5-177683869;