rs114447073

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

Scores

6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11
Variant links:
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]

Genome browser will be placed here

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
KRT81NM_002281.4 linkc.1367C>T p.Pro456Leu missense_variant Exon 9 of 9 ENST00000327741.9 NP_002272.2 Q14533
KRT86NM_001320198.2 linkc.-5+10460G>A intron_variant Intron 2 of 10 ENST00000423955.7 NP_001307127.1 O43790A8K872
KRT86XM_005268866.5 linkc.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
KRT81ENST00000327741.9 linkc.1367C>T p.Pro456Leu missense_variant Exon 9 of 9 1 NM_002281.4 ENSP00000369349.4 Q14533
KRT86ENST00000423955.7 linkc.-5+10460G>A intron_variant Intron 2 of 10 2 NM_001320198.2 ENSP00000444533.1 O43790
KRT86ENST00000553310.6 linkc.-4-15507G>A intron_variant Intron 1 of 2 4 ENSP00000452237.3 U3KPR1

Frequencies

GnomAD3 genomes
AF:
0.00378
AC:
576
AN:
152196
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0134
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000850
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000894
AC:
140
AN:
156552
Hom.:
0
AF XY:
0.000651
AC XY:
54
AN XY:
82888
show subpopulations
Gnomad AFR exome
AF:
0.0141
Gnomad AMR exome
AF:
0.000399
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000436
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000671
Gnomad OTH exome
AF:
0.000226
GnomAD4 exome
AF:
0.000397
AC:
556
AN:
1402268
Hom.:
3
Cov.:
33
AF XY:
0.000341
AC XY:
236
AN XY:
691982
show subpopulations
Gnomad4 AFR exome
AF:
0.0149
Gnomad4 AMR exome
AF:
0.000443
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000554
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000213
Gnomad4 OTH exome
AF:
0.000705
GnomAD4 genome
AF:
0.00379
AC:
578
AN:
152314
Hom.:
6
Cov.:
33
AF XY:
0.00368
AC XY:
274
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0134
Gnomad4 AMR
AF:
0.000849
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000362
Hom.:
1
Bravo
AF:
0.00450
ESP6500AA
AF:
0.0116
AC:
50
ESP6500EA
AF:
0.000238
AC:
2
ExAC
AF:
0.000929
AC:
103
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.96
D;D
MetaRNN
Benign
0.011
T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.6
N;.
REVEL
Uncertain
0.30
Sift
Benign
0.061
T;.
Sift4G
Benign
0.70
T;T
Polyphen
0.95
P;.
Vest4
0.48
MVP
0.68
MPC
0.85
ClinPred
0.019
T
GERP RS
4.8
Varity_R
0.081
gMVP
0.10

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.22
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.22
Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs114447073; hg19: chr12-52680190; COSMIC: COSV100576901; API