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GeneBe

7-101545359-C-T

Variant summary

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

The NM_001278563.3(COL26A1):​c.725C>T​(p.Pro242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,581,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

COL26A1
NM_001278563.3 missense

Scores

1
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL26A1NM_001278563.3 linkuse as main transcriptc.725C>T p.Pro242Leu missense_variant 7/13 ENST00000313669.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL26A1ENST00000313669.12 linkuse as main transcriptc.725C>T p.Pro242Leu missense_variant 7/131 NM_001278563.3 P4Q96A83-1
COL26A1ENST00000613501.1 linkuse as main transcriptc.719C>T p.Pro240Leu missense_variant 7/131 A1Q96A83-2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000606
AC:
13
AN:
214648
Hom.:
0
AF XY:
0.0000587
AC XY:
7
AN XY:
119172
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000918
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:
0.0000147
AC:
21
AN:
1429588
Hom.:
0
Cov.:
32
AF XY:
0.0000141
AC XY:
10
AN XY:
711548
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000479
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.08e-7
Gnomad4 OTH exome
AF:
0.0000340
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.0000581
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 15, 2023The c.719C>T (p.P240L) alteration is located in exon 7 (coding exon 7) of the COL26A1 gene. This alteration results from a C to T substitution at nucleotide position 719, causing the proline (P) at amino acid position 240 to be replaced by a leucine (L). 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
0.14
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Pathogenic
0.86
D
MutationAssessor
Benign
1.3
L;.
MutationTaster
Benign
0.85
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-4.0
D;.
REVEL
Uncertain
0.44
Sift4G
Uncertain
0.014
D;D
Polyphen
1.0
D;.
Vest4
0.60
MVP
0.84
MPC
0.50
ClinPred
0.74
D
GERP RS
5.0
Varity_R
0.23
gMVP
0.27

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs191288309; hg19: chr7-101188640; API