NM_001320198.2:c.340A>G

Variant names:

• chr12-52302256-A-G
• rs61091894
• NM_001320198.2:c.340A>G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PP3_Strong PP5

The NM_001320198.2(KRT86):​c.340A>G​(p.Asn114Asp) 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 Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N114H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 11)
• Consequence: KRT86 NM_001320198.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 9.08
• Publications: 5 publications found

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

ENSG00000287051 (HGNC:58281):

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954
• PP5: Variant 12-52302256-A-G is Pathogenic according to our data. 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT86	NM_001320198.2	c.340A>G	p.Asn114Asp	missense_variant	Exon 3 of 11	ENST00000423955.7	NP_001307127.1
KRT86	XM_005268866.5	c.571A>G	p.Asn191Asp	missense_variant	Exon 3 of 11		XP_005268923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT86	ENST00000423955.7	c.340A>G	p.Asn114Asp	missense_variant	Exon 3 of 11	2	NM_001320198.2	ENSP00000444533.1
KRT86	ENST00000293525.5	c.340A>G	p.Asn114Asp	missense_variant	Exon 1 of 9	1		ENSP00000293525.5
KRT86	ENST00000553310.6	c.340A>G	p.Asn114Asp	missense_variant	Exon 2 of 3	4		ENSP00000452237.3
ENSG00000287051	ENST00000664686.1	n.252-612T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 11

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Monilethrix Pathogenic:1

Aug 01, 1999

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D;D;D
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.87
LIST_S2	Benign	0.82	T;.;T
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.0	.;H;H
PhyloP100		9.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.3	D;D;D
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Vest4		0.0
ClinPred		1.0	D
GERP RS		5.0
PromoterAI		0.0090	Neutral
Varity_R		0.58
gMVP		0.49
Mutation Taster		=0/100	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs61091894; hg19: chr12-52696040;