chr1-85744780-T-A

Position:

• chr1-85744780-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152890.7(COL24A1):​c.4558A>T​(p.Thr1520Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: COL24A1 NM_152890.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL24A1	NM_152890.7	c.4558A>T	p.Thr1520Ser	missense_variant	57/60	ENST00000370571.7	NP_690850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL24A1	ENST00000370571.7	c.4558A>T	p.Thr1520Ser	missense_variant	57/60	1	NM_152890.7	ENSP00000359603	P1
COL24A1	ENST00000426639.5	c.*1945A>T		3_prime_UTR_variant, NMD_transcript_variant	56/59	5		ENSP00000409515
COL24A1	ENST00000473734.1			upstream_gene_variant		4		ENSP00000432605

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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

Jul 26, 2022

The c.4558A>T (p.T1520S) alteration is located in exon 57 (coding exon 57) of the COL24A1 gene. This alteration results from a A to T substitution at nucleotide position 4558, causing the threonine (T) at amino acid position 1520 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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.012	D
Polyphen		0.90	P
Vest4		0.57
MutPred		0.33		Loss of ubiquitination at K1519 (P = 0.0768);
MVP		0.60
MPC		0.24
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.39

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: chr1-86210463;