NM_030976.2:c.175A>C

Variant summary

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

The NM_030976.2(KRTAP4-6):​c.175A>C​(p.Thr59Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,604,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KRTAP4-6
NM_030976.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24
Variant links:
Genes affected
KRTAP4-6 (HGNC:18909): (keratin associated protein 4-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09235853).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP4-6NM_030976.2 linkc.175A>C p.Thr59Pro missense_variant Exon 1 of 1 ENST00000345847.5 NP_112238.1 Q9BYQ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP4-6ENST00000345847.5 linkc.175A>C p.Thr59Pro missense_variant Exon 1 of 1 6 NM_030976.2 ENSP00000328270.5 Q9BYQ5

Frequencies

GnomAD3 genomes
AF:
0.0000405
AC:
6
AN:
148324
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000151
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
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248804
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135216
show subpopulations
Gnomad AFR exome
AF:
0.0000661
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1455610
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
724434
show subpopulations
Gnomad4 AFR exome
AF:
0.0000956
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:
0.0000404
AC:
6
AN:
148426
Hom.:
0
Cov.:
31
AF XY:
0.0000415
AC XY:
3
AN XY:
72262
show subpopulations
Gnomad4 AFR
AF:
0.000151
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
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.175A>C (p.T59P) alteration is located in exon 1 (coding exon 1) of the KRTAP4-6 gene. This alteration results from a A to C substitution at nucleotide position 175, causing the threonine (T) at amino acid position 59 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
19
DANN
Benign
0.45
DEOGEN2
Benign
0.063
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.14
T
M_CAP
Benign
0.00080
T
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.20
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.049
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.11
T
Vest4
0.18
MVP
0.067
MPC
0.068
ClinPred
0.14
T
GERP RS
0.59
Varity_R
0.49
gMVP
0.10

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: rs531460922; hg19: chr17-39296565; COSMIC: COSV61982103; API