rs149495966

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005555.4(KRT6B):​c.1609G>T​(p.Gly537Cys) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KRT6B
NM_005555.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.265
Variant links:
Genes affected
KRT6B (HGNC:6444): (keratin 6B) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. As many as six of this type II cytokeratin (KRT6) have been identified; the multiplicity of the genes is attributed to successive gene duplication events. The genes are expressed with family members KRT16 and/or KRT17 in the filiform papillae of the tongue, the stratified epithelial lining of oral mucosa and esophagus, the outer root sheath of hair follicles, and the glandular epithelia. Mutations in these genes have been associated with pachyonychia congenita. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18385082).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT6BNM_005555.4 linkc.1609G>T p.Gly537Cys missense_variant Exon 9 of 9 ENST00000252252.4 NP_005546.2 P04259

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT6BENST00000252252.4 linkc.1609G>T p.Gly537Cys missense_variant Exon 9 of 9 1 NM_005555.4 ENSP00000252252.3 P04259

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251340
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000274
AC:
4
AN:
1461676
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
16
DANN
Benign
0.94
DEOGEN2
Uncertain
0.48
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.41
T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.18
T
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.19
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.019
D
Polyphen
0.085
B
Vest4
0.24
MutPred
0.41
Gain of catalytic residue at R533 (P = 0.0056);
MVP
0.79
MPC
0.19
ClinPred
0.21
T
GERP RS
1.0
Varity_R
0.46
gMVP
0.66

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149495966; hg19: chr12-52841060; API