chr12-52567100-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_175053.4(KRT74):c.1459G>A(p.Ala487Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,603,648 control chromosomes in the GnomAD database, including 2,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.035 ( 133 hom., cov: 32)
Exomes 𝑓: 0.048 ( 1908 hom. )
Consequence
KRT74
NM_175053.4 missense
NM_175053.4 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: -0.440
Genes affected
KRT74 (HGNC:28929): (keratin 74) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This protein belongs to a family of keratins that are specifically expressed in the inner root sheath of hair follicles.[provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0018889904).
BP6
?
Variant 12-52567100-C-T is Benign according to our data. Variant chr12-52567100-C-T is described in ClinVar as [Benign]. Clinvar id is 1655951.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT74 | NM_175053.4 | c.1459G>A | p.Ala487Thr | missense_variant | 9/9 | ENST00000305620.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT74 | ENST00000305620.3 | c.1459G>A | p.Ala487Thr | missense_variant | 9/9 | 1 | NM_175053.4 | P1 | |
KRT74 | ENST00000549343.5 | c.1501G>A | p.Ala501Thr | missense_variant | 10/10 | 5 | |||
KRT74 | ENST00000546384.1 | n.446G>A | non_coding_transcript_exon_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0347 AC: 5282AN: 152048Hom.: 133 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0331 AC: 8168AN: 247088Hom.: 197 AF XY: 0.0333 AC XY: 4454AN XY: 133704
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GnomAD4 exome AF: 0.0475 AC: 68965AN: 1451484Hom.: 1908 Cov.: 31 AF XY: 0.0463 AC XY: 33337AN XY: 719846
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GnomAD4 genome ? AF: 0.0347 AC: 5277AN: 152164Hom.: 133 Cov.: 32 AF XY: 0.0335 AC XY: 2491AN XY: 74380
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167
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208
ESP6500AA
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38
ESP6500EA
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449
ExAC
?
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3786
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0
.;B
Vest4
MPC
0.063
ClinPred
T
GERP RS
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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