12-52609249-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000305748.7(KRT73):āc.1364T>Cā(p.Ile455Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000645 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000070 ( 0 hom. )
Consequence
KRT73
ENST00000305748.7 missense, splice_region
ENST00000305748.7 missense, splice_region
Scores
5
9
5
Splicing: ADA: 0.06419
2
Clinical Significance
Conservation
PhyloP100: 5.05
Genes affected
KRT73 (HGNC:28928): (keratin 73) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRT73 | NM_175068.3 | c.1364T>C | p.Ile455Thr | missense_variant, splice_region_variant | 8/9 | ENST00000305748.7 | NP_778238.1 | |
KRT73 | XM_047428761.1 | c.1364T>C | p.Ile455Thr | missense_variant, splice_region_variant | 10/11 | XP_047284717.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT73 | ENST00000305748.7 | c.1364T>C | p.Ile455Thr | missense_variant, splice_region_variant | 8/9 | 1 | NM_175068.3 | ENSP00000307014 | P1 | |
KRT73-AS1 | ENST00000551089.5 | n.102-2039A>G | intron_variant, non_coding_transcript_variant | 4 | ||||||
KRT73 | ENST00000552855.1 | c.599T>C | p.Ile200Thr | missense_variant, splice_region_variant | 5/6 | 3 | ENSP00000449081 | |||
KRT73 | ENST00000546934.1 | n.1757T>C | splice_region_variant, non_coding_transcript_exon_variant | 7/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251476Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135908
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GnomAD4 exome AF: 0.0000698 AC: 102AN: 1461294Hom.: 0 Cov.: 30 AF XY: 0.0000646 AC XY: 47AN XY: 727006
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
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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 submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.1364T>C (p.I455T) alteration is located in exon 8 (coding exon 8) of the KRT73 gene. This alteration results from a T to C substitution at nucleotide position 1364, causing the isoleucine (I) at amino acid position 455 to be replaced by a threonine (T). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at