1-85734870-G-A

Variant summary

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

The NM_152890.7(COL24A1):c.4877C>T(p.Pro1626Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL24A1 NM_152890.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

Genes affected

COL24A1 (HGNC:20821): (collagen type XXIV alpha 1 chain) This gene is a member of the collagen gene family and is thought to regulate type I collagen fibrillogenesis during fetal development. [provided by RefSeq, Mar 2017]

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=0.29394603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL24A1	NM_152890.7	c.4877C>T	p.Pro1626Leu	missense_variant	59/60	ENST00000370571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL24A1	ENST00000370571.7	c.4877C>T	p.Pro1626Leu	missense_variant	59/60	1	NM_152890.7	P1
COL24A1	ENST00000426639.5	c.*2264C>T		3_prime_UTR_variant, NMD_transcript_variant	58/59	5
COL24A1	ENST00000473734.1	c.*203C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Apr 07, 2023

The c.4877C>T (p.P1626L) alteration is located in exon 59 (coding exon 59) of the COL24A1 gene. This alteration results from a C to T substitution at nucleotide position 4877, causing the proline (P) at amino acid position 1626 to be replaced by a leucine (L). 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	0.097
BayesDel_addAF	Benign	0.0023	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	19
Dann	Uncertain	0.97
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.020
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.87	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.025	D
Polyphen		0.49	P
Vest4		0.11
MutPred		0.50		Gain of catalytic residue at P1626 (P = 0.0064);
MVP		0.69
MPC		0.035
ClinPred		0.56	D
GERP RS		4.3
Varity_R		0.19
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-86200553;