rs114447073
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002281.4(KRT81):c.1367C>T(p.Pro456Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000729 in 1,554,582 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0038 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00040 ( 3 hom. )
Consequence
KRT81
NM_002281.4 missense
NM_002281.4 missense
Scores
6
12
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.11
Genes affected
KRT81 (HGNC:6458): (keratin 81) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin, as well as KRTHB3 and KRTHB6, is found primarily in the hair cortex. Mutations in this gene and KRTHB6 have been observed in patients with a rare dominant hair disease, monilethrix. Some human genome assemblies (example T2T-CHM13) have a non-coding version of the gene due to the presence of a SNP that introduces a premature stop codon after codon 281. [provided by RefSeq, Jan 2024]
KRT86 (HGNC:6463): (keratin 86) This gene encodes a type II keratin protein, which heterodimerizes with type I keratins to form hair and nails. This gene is present in a cluster of related genes and pseudogenes on chromosome 12. Mutations in this gene have been observed in patients with the hair disease monilethrix. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 578 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRT81 | NM_002281.4 | c.1367C>T | p.Pro456Leu | missense_variant | Exon 9 of 9 | ENST00000327741.9 | NP_002272.2 | |
KRT86 | NM_001320198.2 | c.-5+10460G>A | intron_variant | Intron 2 of 10 | ENST00000423955.7 | NP_001307127.1 | ||
KRT86 | XM_005268866.5 | c.129+10460G>A | intron_variant | Intron 2 of 10 | XP_005268923.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT81 | ENST00000327741.9 | c.1367C>T | p.Pro456Leu | missense_variant | Exon 9 of 9 | 1 | NM_002281.4 | ENSP00000369349.4 | ||
KRT86 | ENST00000423955.7 | c.-5+10460G>A | intron_variant | Intron 2 of 10 | 2 | NM_001320198.2 | ENSP00000444533.1 | |||
KRT86 | ENST00000553310.6 | c.-4-15507G>A | intron_variant | Intron 1 of 2 | 4 | ENSP00000452237.3 |
Frequencies
GnomAD3 genomes AF: 0.00378 AC: 576AN: 152196Hom.: 5 Cov.: 33
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GnomAD3 exomes AF: 0.000894 AC: 140AN: 156552Hom.: 0 AF XY: 0.000651 AC XY: 54AN XY: 82888
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GnomAD4 exome AF: 0.000397 AC: 556AN: 1402268Hom.: 3 Cov.: 33 AF XY: 0.000341 AC XY: 236AN XY: 691982
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GnomAD4 genome AF: 0.00379 AC: 578AN: 152314Hom.: 6 Cov.: 33 AF XY: 0.00368 AC XY: 274AN XY: 74492
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at