1-85783525-A-G

Position:

• chr1-85783525-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152890.7(COL24A1):​c.4255T>C​(p.Ser1419Pro) 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. 14/21 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: 0.885

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11416888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL24A1	NM_152890.7	c.4255T>C	p.Ser1419Pro	missense_variant	51/60	ENST00000370571.7	NP_690850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL24A1	ENST00000370571.7	c.4255T>C	p.Ser1419Pro	missense_variant	51/60	1	NM_152890.7	ENSP00000359603	P1
COL24A1	ENST00000426639.5	c.*1705T>C		3_prime_UTR_variant, NMD_transcript_variant	52/59	5		ENSP00000409515

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 07, 2024

The c.4255T>C (p.S1419P) alteration is located in exon 51 (coding exon 51) of the COL24A1 gene. This alteration results from a T to C substitution at nucleotide position 4255, causing the serine (S) at amino acid position 1419 to be replaced by a proline (P). 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	0.069
BayesDel_addAF	Benign	-0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.66	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.31
Sift	Benign	0.11	T
Sift4G	Benign	0.26	T
Polyphen		0.0040	B
Vest4		0.20
MutPred		0.22		Loss of glycosylation at S1419 (P = 0.0155);
MVP		0.51
MPC		0.038
ClinPred		0.23	T
GERP RS		1.5
Varity_R		0.20
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-86249208;