chr10-104057158-C-G

Position:

• chr10-104057158-C-G

Variant summary

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

The NM_000494.4(COL17A1):​c.1282G>C​(p.Gly428Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G428S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL17A1 NM_000494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.699

Genes affected

COL17A1 (HGNC:2194): (collagen type XVII alpha 1 chain) This gene encodes the alpha chain of type XVII collagen. Unlike most collagens, collagen XVII is a transmembrane protein. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes at the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Mutations in this gene are associated with both generalized atrophic benign and junctional epidermolysis bullosa. Two homotrimeric forms of type XVII collagen exist. The full length form is the transmembrane protein. A soluble form, referred to as either ectodomain or LAD-1, is generated by proteolytic processing of the full length form. [provided by RefSeq, Jul 2008]

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=0.07719654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4	c.1282G>C	p.Gly428Arg	missense_variant	17/56	ENST00000648076.2	NP_000485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2	c.1282G>C	p.Gly428Arg	missense_variant	17/56		NM_000494.4	ENSP00000497653.1
COL17A1	ENST00000369733.8	c.1282G>C	p.Gly428Arg	missense_variant	16/51	5		ENSP00000358748.3
COL17A1	ENST00000650263.1	c.1234G>C	p.Gly412Arg	missense_variant	16/22			ENSP00000497850.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.8
DANN	Benign	0.68
DEOGEN2	Benign	0.29	.;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.52	T;.;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.0	L;L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N;N;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.015	D;D;.;.
Sift4G	Benign	0.13	T;T;.;.
Polyphen		0.27	B;B;B;.
Vest4		0.25
MutPred		0.20		Gain of methylation at G428 (P = 0.0113);Gain of methylation at G428 (P = 0.0113);Gain of methylation at G428 (P = 0.0113);.;
MVP		0.56
MPC		0.078
ClinPred		0.15	T
GERP RS		1.7
Varity_R		0.042
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs805698; hg19: chr10-105816916;