chr12-52692802-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_175078.3(KRT77):c.1159C>T(p.Arg387Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,604,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000060 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000036 ( 2 hom. )
Consequence
KRT77
NM_175078.3 missense
NM_175078.3 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 2.31
Genes affected
KRT77 (HGNC:20411): (keratin 77) 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 an epithelial keratin that is expressed in the skin and eccrine sweat glands. 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.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.918
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT77 | NM_175078.3 | c.1159C>T | p.Arg387Cys | missense_variant | 6/9 | ENST00000341809.8 | |
KRT77 | XM_011538288.3 | c.460C>T | p.Arg154Cys | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT77 | ENST00000341809.8 | c.1159C>T | p.Arg387Cys | missense_variant | 6/9 | 1 | NM_175078.3 | P1 | |
KRT77 | ENST00000553168.1 | c.*497C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/10 | 1 | ||||
ENST00000547533.1 | n.193+5G>A | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | 3 | ||||||
KRT77 | ENST00000550823.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000598 AC: 9AN: 150446Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250222Hom.: 1 AF XY: 0.0000370 AC XY: 5AN XY: 135204
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GnomAD4 exome AF: 0.0000365 AC: 53AN: 1453636Hom.: 2 Cov.: 32 AF XY: 0.0000373 AC XY: 27AN XY: 723174
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GnomAD4 genome ? AF: 0.0000598 AC: 9AN: 150446Hom.: 0 Cov.: 31 AF XY: 0.0000408 AC XY: 3AN XY: 73506
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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 05, 2023 | The c.1159C>T (p.R387C) alteration is located in exon 6 (coding exon 6) of the KRT77 gene. This alteration results from a C to T substitution at nucleotide position 1159, causing the arginine (R) at amino acid position 387 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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