1-85730589-T-A

Variant names:

• chr1-85730589-T-A
• NM_152890.7:c.5102A>T

Variant summary

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

The NM_152890.7(COL24A1):​c.5102A>T​(p.Glu1701Val) 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: 33)
• Consequence: COL24A1 NM_152890.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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=0.20744845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL24A1	NM_152890.7	c.5102A>T	p.Glu1701Val	missense_variant	Exon 60 of 60	ENST00000370571.7	NP_690850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL24A1	ENST00000370571.7	c.5102A>T	p.Glu1701Val	missense_variant	Exon 60 of 60	1	NM_152890.7	ENSP00000359603.2
COL24A1	ENST00000426639.5	n.*2489A>T		non_coding_transcript_exon_variant	Exon 59 of 59	5		ENSP00000409515.1
COL24A1	ENST00000426639.5	n.*2489A>T		3_prime_UTR_variant	Exon 59 of 59	5		ENSP00000409515.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5102A>T (p.E1701V) alteration is located in exon 60 (coding exon 60) of the COL24A1 gene. This alteration results from a A to T substitution at nucleotide position 5102, causing the glutamic acid (E) at amino acid position 1701 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.017	D
Polyphen		0.46	P
Vest4		0.20
MutPred		0.64		Loss of disorder (P = 0.0065);
MVP		0.64
MPC		0.069
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.12
gMVP		0.42

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: chr1-86196272;