10-104032256-T-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000494.4(COL17A1):c.4473A>T(p.Arg1491Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
COL17A1
NM_000494.4 missense
NM_000494.4 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 0.626
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.20934609).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL17A1 | NM_000494.4 | c.4473A>T | p.Arg1491Ser | missense_variant | 56/56 | ENST00000648076.2 | NP_000485.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL17A1 | ENST00000648076.2 | c.4473A>T | p.Arg1491Ser | missense_variant | 56/56 | NM_000494.4 | ENSP00000497653 | A2 | ||
COL17A1 | ENST00000369733.8 | c.4227A>T | p.Arg1409Ser | missense_variant | 51/51 | 5 | ENSP00000358748 | P4 | ||
COL17A1 | ENST00000433822.1 | c.180A>T | p.Arg60Ser | missense_variant | 3/4 | 5 | ENSP00000388832 | |||
COL17A1 | ENST00000647647.1 | c.*543A>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | ENSP00000497865 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251412Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135884
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GnomAD4 exome AF: 0.000106 AC: 155AN: 1461686Hom.: 0 Cov.: 30 AF XY: 0.000116 AC XY: 84AN XY: 727172
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 10, 2023 | The c.4473A>T (p.R1491S) alteration is located in exon 56 (coding exon 55) of the COL17A1 gene. This alteration results from a A to T substitution at nucleotide position 4473, causing the arginine (R) at amino acid position 1491 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Benign
T;D;.
Sift4G
Uncertain
D;D;.
Polyphen
0.91
.;P;P
Vest4
MutPred
0.44
.;Gain of phosphorylation at R1491 (P = 0.0019);Gain of phosphorylation at R1491 (P = 0.0019);
MVP
MPC
0.074
ClinPred
T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at