Genetic Variant KRTAP16-1:p.Val396Phe (chr17-41308068-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001146182.2(KRTAP16-1):c.1186G>T(p.Val396Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,550,516 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

KRTAP16-1
NM_001146182.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.975

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=0.036489695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP16-1	NM_001146182.2 link	c.1186G>T	p.Val396Phe	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
KRTAP16-1	ENST00000391352.2 link	c.1186G>T	p.Val396Phe	missense_variant	Exon 1 of 1	6	NM_001146182.2	ENSP00000375147.1		A8MUX0

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000201

AC:

AN:

149378

Hom.:

AF XY:

0.000187

AC XY:

AN XY:

80392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000238

Gnomad NFE exome

AF:

0.000399

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000375

AC:

524

AN:

1398354

Hom.:

Cov.:

AF XY:

0.000383

AC XY:

264

AN XY:

689700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.000290

Gnomad4 NFE exome

AF:

0.000448

Gnomad4 OTH exome

AF:

0.000276

GnomAD4 genome

AF:

0.000164

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000131

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1186G>T (p.V396F) alteration is located in exon 1 (coding exon 1) of the KRTAP16-1 gene. This alteration results from a G to T substitution at nucleotide position 1186, causing the valine (V) at amino acid position 396 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.66

DANN

Benign

0.88

DEOGEN2

Benign

0.0043

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.032

M_CAP

Benign

0.00062

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.82

REVEL

Benign

0.019

Sift

Uncertain

0.021

Sift4G

Benign

0.068

Vest4

0.13

MVP

0.072

ClinPred

0.022

GERP RS

-2.8

Varity_R

0.045

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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