7-101447692-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001278563.3(COL26A1):c.290C>T(p.Thr97Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL26A1 NM_001278563.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

Genes affected

COL26A1 (HGNC:18038): (collagen type XXVI alpha 1 chain) This gene encodes a protein containing an emilin domain and two collagen stretches. This gene may be associated with aspirin-intolerant asthma. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL26A1	NM_001278563.3	c.290C>T	p.Thr97Ile	missense_variant	3/13	ENST00000313669.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL26A1	ENST00000313669.12	c.290C>T	p.Thr97Ile	missense_variant	3/13	1	NM_001278563.3	P4
COL26A1	ENST00000613501.1	c.284C>T	p.Thr95Ile	missense_variant, splice_region_variant	3/13	1		A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

May 04, 2022

The c.284C>T (p.T95I) alteration is located in exon 3 (coding exon 3) of the COL26A1 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the threonine (T) at amino acid position 95 to be replaced by an isoleucine (I). 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	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.091	T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.82	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.6	D;.
REVEL	Uncertain	0.34
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.90
MutPred		0.72		Loss of MoRF binding (P = 0.136);.;
MVP		0.87
MPC		0.33
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.49
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-101090973;