Variant rs371683842 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002281.4(KRT81):c.1324G>C(p.Val442Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

KRT81
NM_002281.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

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]

KRT81 links:

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]

KRT86 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078755885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT81	NM_002281.4 link	c.1324G>C	p.Val442Leu	missense_variant	Exon 9 of 9	ENST00000327741.9	NP_002272.2	Q14533
KRT86	NM_001320198.2 link	c.-5+10503C>G		intron_variant	Intron 2 of 10	ENST00000423955.7	NP_001307127.1	O43790A8K872
KRT86	XM_005268866.5 link	c.129+10503C>G		intron_variant	Intron 2 of 10		XP_005268923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRT81	ENST00000327741.9 link	c.1324G>C	p.Val442Leu	missense_variant	Exon 9 of 9	1	NM_002281.4	ENSP00000369349.4	Q14533
KRT86	ENST00000423955.7 link	c.-5+10503C>G		intron_variant	Intron 2 of 10	2	NM_001320198.2	ENSP00000444533.1	O43790
KRT86	ENST00000553310.6 link	c.-4-15464C>G		intron_variant	Intron 1 of 2	4		ENSP00000452237.3	U3KPR1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1400486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.26e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.040

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.11

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.83

N;.

REVEL

Benign

0.19

Sift

Benign

0.21

T;.

Sift4G

Benign

0.79

T;T

Polyphen

0.0010

B;.

Vest4

0.21

MutPred

0.43

Gain of catalytic residue at V442 (P = 0);Gain of catalytic residue at V442 (P = 0);

MVP

0.22

MPC

0.37

ClinPred

0.096

GERP RS

2.5

Varity_R

0.096

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over