7-7360456-T-C

Variant summary

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

The NM_001037763.3(COL28A1):c.3139A>G(p.Thr1047Ala) 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: COL28A1 NM_001037763.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.139

Genes affected

COL28A1 (HGNC:22442): (collagen type XXVIII alpha 1 chain) COL28A1 belongs to a class of collagens containing von Willebrand factor (VWF; MIM 613160) type A (VWFA) domains (Veit et al., 2006 [PubMed 16330543]).[supplied by OMIM, Nov 2010]

LOC107986764 (HGNC:):

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=0.0737229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL28A1	NM_001037763.3	c.3139A>G	p.Thr1047Ala	missense_variant	34/35	ENST00000399429.8
LOC107986764	XR_002956539.2	n.442-16105T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL28A1	ENST00000399429.8	c.3139A>G	p.Thr1047Ala	missense_variant	34/35	1	NM_001037763.3	P1
COL28A1	ENST00000453441.1	c.4A>G	p.Thr2Ala	missense_variant	1/3	2
COL28A1	ENST00000430711.5	c.190A>G	p.Thr64Ala	missense_variant, NMD_transcript_variant	2/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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.3139A>G (p.T1047A) alteration is located in exon 34 (coding exon 33) of the COL28A1 gene. This alteration results from a A to G substitution at nucleotide position 3139, causing the threonine (T) at amino acid position 1047 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	5.3
Dann	Benign	0.72
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.72	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.010	D;T
Sift4G	Uncertain	0.056	T;T
Polyphen		0.0060	.;B
Vest4		0.25
MutPred		0.20		.;Loss of glycosylation at T1047 (P = 0.0018);
MVP		0.25
MPC		0.029
ClinPred		0.067	T
GERP RS		-0.15
Varity_R		0.034
gMVP		0.22

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: chr7-7400087;