1-85737479-C-A

Variant names:

• chr1-85737479-C-A
• rs747191081
• NM_152890.7:c.4699G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_152890.7(COL24A1):​c.4699G>T​(p.Gly1567Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,611,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1567V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: COL24A1 NM_152890.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 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.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

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.4699G>T	p.Gly1567Cys	missense	Exon 58 of 60	NP_690850.2	Q17RW2-1
	COL24A1	NM_001349955.1		c.2599G>T	p.Gly867Cys	missense	Exon 58 of 60	NP_001336884.1
	COL24A1	NR_146340.2		n.4848G>T		non_coding_transcript_exon	Exon 59 of 61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	ENST00000370571.7	TSL:1 MANE Select	c.4699G>T	p.Gly1567Cys	missense	Exon 58 of 60	ENSP00000359603.2	Q17RW2-1
	COL24A1	ENST00000426639.5	TSL:5	n.*2086G>T		non_coding_transcript_exon	Exon 57 of 59	ENSP00000409515.1	F8WDM8
	COL24A1	ENST00000473734.1	TSL:4	n.109G>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000432605.1	H0YCZ7

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151908 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 29 AN: 247180 AF XY: 0.0000894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000815

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1459920 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21 AN XY: 726326

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.000761 AC: 34 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110858

Other (OTH) AF: 0.0000332 AC: 2 AN: 60250

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151908 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74172

African (AFR) AF: 0.0000242 AC: 1 AN: 41356

American (AMR) AF: 0.000131 AC: 2 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000197 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000910 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.3	H
PhyloP100		7.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.82		Loss of sheet (P = 0.0104)
MVP		0.65
MPC		0.26
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.80
gMVP		0.85
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.46		Position offset: -13
DS_AL_spliceai		0.41		Position offset: 26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747191081; hg19: chr1-86203162;