10-69802525-G-T

Variant names:

• chr10-69802525-G-T
• NM_001368882.1:c.102G>T

Variant summary

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

The NM_001368882.1(COL13A1):​c.102G>T​(p.Glu34Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL13A1 NM_001368882.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

Genes affected

COL13A1 (HGNC:2190): (collagen type XIII alpha 1 chain) This gene encodes the alpha chain of one of the nonfibrillar collagens. The function of this gene product is not known, however, it has been detected at low levels in all connective tissue-producing cells so it may serve a general function in connective tissues. Unlike most of the collagens, which are secreted into the extracellular matrix, collagen XIII contains a transmembrane domain and the protein has been localized to the plasma membrane. The transcripts for this gene undergo complex and extensive splicing involving at least eight exons. Like other collagens, collagen XIII is a trimer; it is not known whether this trimer is composed of one or more than one alpha chain isomer. A number of alternatively spliced transcript variants have been described, but the full length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

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 rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.102G>T	p.Glu34Asp	missense_variant	Exon 1 of 41	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.102G>T	p.Glu34Asp	missense_variant	Exon 1 of 41		NM_001368882.1	ENSP00000496051.1

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 provided Uncertain:1

Jul 27, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glutamic acid with aspartic acid at codon 34 of the COL13A1 protein (p.Glu34Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL13A1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	.;T;.;.;.;T;.;.;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.84	T;D;D;D;T;T;D;T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	0.34	.;N;N;N;N;.;N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.11	.;N;N;N;N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.031	.;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.053	.;T;T;T;T;T;T;T;T
Polyphen		0.96, 0.88	.;P;P;P;.;.;P;P;.
Vest4		0.18, 0.22, 0.23, 0.24, 0.25, 0.32, 0.30, 0.30
MutPred		0.27		Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);Loss of methylation at R32 (P = 0.1146);
MVP		0.83
MPC		2.3
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.15
gMVP		0.13

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: chr10-71562281;