1-85737410-C-G

Position:

• chr1-85737410-C-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.4768G>C​(p.Val1590Leu) 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. 16/21 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: -0.0920

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=0.09397337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL24A1	NM_152890.7	c.4768G>C	p.Val1590Leu	missense_variant	58/60	ENST00000370571.7	NP_690850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL24A1	ENST00000370571.7	c.4768G>C	p.Val1590Leu	missense_variant	58/60	1	NM_152890.7	ENSP00000359603	P1
COL24A1	ENST00000473734.1	c.181G>C	p.Val61Leu	missense_variant, NMD_transcript_variant	2/4	4		ENSP00000432605
COL24A1	ENST00000426639.5	c.*2155G>C		3_prime_UTR_variant, NMD_transcript_variant	57/59	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

Sep 29, 2022

The c.4768G>C (p.V1590L) alteration is located in exon 58 (coding exon 58) of the COL24A1 gene. This alteration results from a G to C substitution at nucleotide position 4768, causing the valine (V) at amino acid position 1590 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	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.9
DANN	Benign	0.89
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.93	D;D
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.078
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		0.11	B
Vest4		0.095
MutPred		0.62		Gain of ubiquitination at K1594 (P = 0.1162);
MVP		0.36
MPC		0.034
ClinPred		0.19	T
GERP RS		1.8
Varity_R		0.076
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-86203093;