Genetic Variant NM_001320198.2:c.340A>C (chr12-52302256-A-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM5PP3_Strong

The NM_001320198.2(KRT86):c.340A>C(p.Asn114His) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N114D) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 11)

Failed GnomAD Quality Control

Consequence

KRT86
NM_001320198.2 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 9.08

Publications

5 publications found

Variant links:

Genes affected

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 Gene-Disease associations (from GenCC):

monilethrix
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet
monilethrix-1
Inheritance: AD Classification: MODERATE Submitted by: G2P

KRT86 links:

ENSG00000287051 (HGNC:58281):

ENSG00000287051 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr12-52302256-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 7612.Status of the report is no_assertion_criteria_provided, 0 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.957

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320198.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT86	NM_001320198.2	MANE Select	c.340A>C	p.Asn114His	missense	Exon 3 of 11	NP_001307127.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KRT86	ENST00000423955.7	TSL:2 MANE Select	c.340A>C	p.Asn114His	missense	Exon 3 of 11	ENSP00000444533.1
KRT86	ENST00000293525.5	TSL:1	c.340A>C	p.Asn114His	missense	Exon 1 of 9	ENSP00000293525.5
KRT86	ENST00000553310.6	TSL:4	c.340A>C	p.Asn114His	missense	Exon 2 of 3	ENSP00000452237.3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

93016

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

93016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

42228

African (AFR)

AF:

0.00

AC:

AN:

22720

American (AMR)

AF:

0.00

AC:

AN:

8790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2588

East Asian (EAS)

AF:

0.00

AC:

AN:

3444

South Asian (SAS)

AF:

0.00

AC:

AN:

2394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

45942

Other (OTH)

AF:

0.00

AC:

AN:

1172

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Epithelial Biology; Institute of Medical Biology, Singapore

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.8

PhyloP100

9.1

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.99

MutPred

0.83

Gain of catalytic residue at A118 (P = 0.0159)

MVP

0.96

MPC

2.1

ClinPred

1.0

GERP RS

5.0

PromoterAI

-0.058

Neutral

(source)

Varity_R

0.59

gMVP

0.49

Mutation Taster

=2/98

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over