17-41460117-C-T

Variant summary

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

The NM_002278.3(KRT32):​c.1340G>A​(p.Arg447His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,605,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R447L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

KRT32
NM_002278.3 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.198
Variant links:
Genes affected
KRT32 (HGNC:6449): (keratin 32) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.09325874).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT32NM_002278.3 linkc.1340G>A p.Arg447His missense_variant Exon 7 of 7 ENST00000225899.4 NP_002269.3 Q14532

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT32ENST00000225899.4 linkc.1340G>A p.Arg447His missense_variant Exon 7 of 7 1 NM_002278.3 ENSP00000225899.3 Q14532

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000124
AC:
3
AN:
242774
Hom.:
0
AF XY:
0.00000762
AC XY:
1
AN XY:
131212
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000274
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1453520
Hom.:
0
Cov.:
30
AF XY:
0.0000166
AC XY:
12
AN XY:
722660
show subpopulations
Gnomad4 AFR exome
AF:
0.0000601
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000394
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
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
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.030
T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.57
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.093
T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.12
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.013
B
Vest4
0.12
MutPred
0.35
Loss of methylation at R447 (P = 0.0545);
MVP
0.61
MPC
0.15
ClinPred
0.20
T
GERP RS
1.6
Varity_R
0.14
gMVP
0.46

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: rs764794620; hg19: chr17-39616369; COSMIC: COSV56787702; API