rs121909130

Positions:

• chr12-52306272-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001320198.2(KRT86):​c.1239G>T​(p.Glu413Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT86 NM_001320198.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 1.73

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]

(HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949
• PP5: Variant 12-52306272-G-T is Pathogenic according to our data. Variant chr12-52306272-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 7610.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT86	NM_001320198.2	c.1239G>T	p.Glu413Asp	missense_variant	9/11	ENST00000423955.7	NP_001307127.1
KRT86	XM_005268866.5	c.1470G>T	p.Glu490Asp	missense_variant	9/11		XP_005268923.1
KRT81	XM_047428838.1	c.-14517C>A		5_prime_UTR_variant	1/10		XP_047284794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT86	ENST00000423955.7	c.1239G>T	p.Glu413Asp	missense_variant	9/11	2	NM_001320198.2	ENSP00000444533	P1
KRT86	ENST00000293525.5	c.1239G>T	p.Glu413Asp	missense_variant	7/9	1		ENSP00000293525	P1
	ENST00000664686.1	n.16C>A		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Beaded hair Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 1998

- -

not provided Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	D;D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.64	.;T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.1	H;H
MutationTaster	Benign	0.75	A
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.77		Gain of catalytic residue at L417 (P = 0.001);Gain of catalytic residue at L417 (P = 0.001);
MVP		0.91
MPC		0.40
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.42
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs121909130; hg19: chr12-52700056;