rs17655565

Variant names:

• chr12-52298174-T-C
• rs17655565
• NM_001320198.2:c.-4-3739T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000423955.7(KRT86):​c.-4-3739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,220 control chromosomes in the GnomAD database, including 1,321 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 0.13 (1321 hom., cov: 33)
• Consequence: KRT86 ENST00000423955.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000423955.7. 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.-4-3739T>C		intron	N/A	NP_001307127.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT86	ENST00000423955.7	TSL:2 MANE Select	c.-4-3739T>C		intron	N/A	ENSP00000444533.1
	KRT86	ENST00000553310.6	TSL:4	c.-4-3739T>C		intron	N/A	ENSP00000452237.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19500 AN: 152102 Hom.: 1321 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19519 AN: 152220 Hom.: 1321 Cov.: 33 AF XY: 0.128 AC XY: 9555 AN XY: 74432

African (AFR) AF: 0.169 AC: 7010 AN: 41522

American (AMR) AF: 0.0802 AC: 1227 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 232 AN: 3472

East Asian (EAS) AF: 0.123 AC: 638 AN: 5184

South Asian (SAS) AF: 0.0959 AC: 462 AN: 4818

European-Finnish (FIN) AF: 0.154 AC: 1631 AN: 10602

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.116 AC: 7908 AN: 68010

Other (OTH) AF: 0.116 AC: 244 AN: 2110

Alfa AF: 0.112 Hom.: 1796

Bravo AF: 0.123

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.83
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs17655565; hg19: chr12-52691958;