Variant chr17-41117985-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033059.4(KRTAP4-11):c.331C>T(p.Arg111Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,491,592 control chromosomes in the GnomAD database, including 7 homozygotes. 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 0.00018 ( 3 hom., cov: 30)

Exomes 𝑓: 0.000029 ( 4 hom. )

Consequence

KRTAP4-11
NM_033059.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.55

Variant links:

Genes affected

KRTAP4-11 (HGNC:18911): (keratin associated protein 4-11) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Mar 2009]

KRTAP4-11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057758152).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-11	NM_033059.4 linkuse as main transcript	c.331C>T	p.Arg111Cys	missense_variant	1/1	ENST00000391413.4	NP_149048.2	Q9BYQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-11	ENST00000391413.4 linkuse as main transcript	c.331C>T	p.Arg111Cys	missense_variant	1/1	6	NM_033059.4	ENSP00000375232.2		Q9BYQ6

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

147292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000663

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000201

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:

0.0000527

AC:

AN:

246712

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

134448

show subpopulations

Gnomad AFR exome

AF:

0.0000696

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000610

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1344300

Hom.:

Cov.:

196

AF XY:

0.0000347

AC XY:

AN XY:

663422

show subpopulations

Gnomad4 AFR exome

AF:

0.000242

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000337

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000554

GnomAD4 genome

AF:

0.000177

AC:

AN:

147292

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

AN XY:

71882

show subpopulations

Gnomad4 AFR

AF:

0.000663

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000603

AC:

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 08, 2023

The c.331C>T (p.R111C) alteration is located in exon 1 (coding exon 1) of the KRTAP4-11 gene. This alteration results from a C to T substitution at nucleotide position 331, causing the arginine (R) at amino acid position 111 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

0.25

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.019

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.19

M_CAP

Benign

0.0051

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.058

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0080

Polyphen

0.46

Vest4

0.11

MVP

0.18

MPC

0.0083

ClinPred

0.34

GERP RS

-2.4

Varity_R

0.38

gMVP

0.077

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