1-85744725-C-A

Variant names:

• chr1-85744725-C-A
• rs371171500
• NM_152890.7:c.4613G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152890.7(COL24A1):​c.4613G>T​(p.Arg1538Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1538Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: COL24A1 NM_152890.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

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]

COL24A1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152890.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	NM_152890.7	MANE Select	c.4613G>T	p.Arg1538Leu	missense	Exon 57 of 60	NP_690850.2	Q17RW2-1
	COL24A1	NM_001349955.1		c.2513G>T	p.Arg838Leu	missense	Exon 57 of 60	NP_001336884.1
	COL24A1	NR_146340.2		n.4762G>T		non_coding_transcript_exon	Exon 58 of 61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	ENST00000370571.7	TSL:1 MANE Select	c.4613G>T	p.Arg1538Leu	missense	Exon 57 of 60	ENSP00000359603.2	Q17RW2-1
	COL24A1	ENST00000426639.5	TSL:5	n.*2000G>T		non_coding_transcript_exon	Exon 56 of 59	ENSP00000409515.1	F8WDM8
	COL24A1	ENST00000473734.1	TSL:4	n.23G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000432605.1	H0YCZ7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.46		Loss of disorder (P = 0.0506)
MVP		0.60
MPC		0.26
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.62
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs371171500; hg19: chr1-86210408;