rs529097672

Variant summary

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

The NM_001146182.2(KRTAP16-1):​c.1265G>T​(p.Arg422Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R422H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

KRTAP16-1
NM_001146182.2 missense

Scores

6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99
Variant links:
Genes affected
KRTAP16-1 (HGNC:18916): (keratin associated protein 16-1) 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=0.21464539).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRTAP16-1NM_001146182.2 linkc.1265G>T p.Arg422Leu missense_variant Exon 1 of 1 ENST00000391352.2 NP_001139654.1 A8MUX0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRTAP16-1ENST00000391352.2 linkc.1265G>T p.Arg422Leu missense_variant Exon 1 of 1 6 NM_001146182.2 ENSP00000375147.1 A8MUX0

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152036
Hom.:
0
Cov.:
32
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
GnomAD4 exome
Cov.:
38
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152036
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74258
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
Uncertain
0.39
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
T
Eigen
Benign
0.086
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.80
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
0.81
L
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.19
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.073
T
Vest4
0.32
MutPred
0.52
Loss of disorder (P = 0.0275);
MVP
0.40
ClinPred
0.95
D
GERP RS
5.0
Varity_R
0.31
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs529097672; hg19: chr17-39464241; API