rs57802288

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000293670.3(KRT83):​c.1219G>T​(p.Glu407Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KRT83
ENST00000293670.3 stop_gained

Scores

5
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.80
Variant links:
Genes affected
KRT83 (HGNC:6460): (keratin 83) 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 KRTHB1 and KRTHB6, is found primarily in the hair cortex. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRT83NM_002282.3 linkuse as main transcriptc.1219G>T p.Glu407Ter stop_gained 7/9 ENST00000293670.3 NP_002273.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRT83ENST00000293670.3 linkuse as main transcriptc.1219G>T p.Glu407Ter stop_gained 7/91 NM_002282.3 ENSP00000293670 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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
AF:
6.85e-7
AC:
1
AN:
1460520
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726572
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
50
DANN
Uncertain
1.0
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A
Vest4
0.25
GERP RS
3.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs57802288; hg19: chr12-52709720; API