Variant 17-41307906-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001146182.2(KRTAP16-1):c.1348C>T(p.Arg450Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000089 in 1,550,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

KRTAP16-1
NM_001146182.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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]

KRTAP16-1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008969218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP16-1	NM_001146182.2 linkuse as main transcript	c.1348C>T	p.Arg450Cys	missense_variant	1/1	ENST00000391352.2	NP_001139654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP16-1	ENST00000391352.2 linkuse as main transcript	c.1348C>T	p.Arg450Cys	missense_variant	1/1		NM_001146182.2	ENSP00000375147	P1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000386

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:

0.000222

AC:

AN:

148738

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

80004

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.0000926

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.0000887

AC:

124

AN:

1398368

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

689694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00353

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000139

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.000170

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1348C>T (p.R450C) alteration is located in exon 1 (coding exon 1) of the KRTAP16-1 gene. This alteration results from a C to T substitution at nucleotide position 1348, causing the arginine (R) at amino acid position 450 to be replaced by a cysteine (C). 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

0.094

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.011

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.1

REVEL

Benign

0.080

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Vest4

0.093

MutPred

0.40

Gain of catalytic residue at S452 (P = 0.0256);

MVP

0.38

ClinPred

0.098

GERP RS

2.3

Varity_R

0.098

gMVP

0.064

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over