7-101544030-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001278563.3(COL26A1):c.637G>C(p.Ala213Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL26A1 NM_001278563.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36236843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL26A1	NM_001278563.3	c.637G>C	p.Ala213Pro	missense_variant	6/13	ENST00000313669.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL26A1	ENST00000313669.12	c.637G>C	p.Ala213Pro	missense_variant	6/13	1	NM_001278563.3	P4
COL26A1	ENST00000613501.1	c.631G>C	p.Ala211Pro	missense_variant	6/13	1		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000925 AC: 2 AN: 216104 Hom.: 0 AF XY: 0.00000850 AC XY: 1 AN XY: 117602

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000122

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444224 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 25, 2023

The c.631G>C (p.A211P) alteration is located in exon 6 (coding exon 6) of the COL26A1 gene. This alteration results from a G to C substitution at nucleotide position 631, causing the alanine (A) at amino acid position 211 to be replaced by a proline (P). 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	0.089
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Uncertain	0.020
Cadd	Benign	20
Dann	Benign	0.95
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	-1.3	N;.
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.40	N;.
REVEL	Benign	0.28
Sift4G	Benign	0.53	T;T
Polyphen		1.0	D;.
Vest4		0.33
MutPred		0.28		Gain of glycosylation at A213 (P = 0.0059);.;
MVP		0.85
MPC		0.15
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.29
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs764856083; hg19: chr7-101187311;