Variant 17-41084529-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033061.4(KRTAP4-7):c.323C>A(p.Thr108Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 4)

Exomes 𝑓: 0.000065 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP4-7
NM_033061.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.47

Variant links:

Genes affected

KRTAP4-7 (HGNC:18898): (keratin associated protein 4-7) 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]

KRTAP4-7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0112454295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-7	NM_033061.4 linkuse as main transcript	c.323C>A	p.Thr108Asn	missense_variant	1/1	ENST00000391417.6	NP_149050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-7	ENST00000391417.6 linkuse as main transcript	c.323C>A	p.Thr108Asn	missense_variant	1/1		NM_033061.4	ENSP00000375236	P1

Frequencies

GnomAD3 genomes

AF:

0.000196

AC:

AN:

61260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000163

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000345

Gnomad SAS

AF:

0.000445

Gnomad FIN

AF:

0.000262

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000371

Gnomad OTH

AF:

0.00121

GnomAD3 exomes

AF:

0.00141

AC:

275

AN:

194544

Hom.:

AF XY:

0.00118

AC XY:

126

AN XY:

106398

show subpopulations

Gnomad AFR exome

AF:

0.00924

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.000599

Gnomad EAS exome

AF:

0.00519

Gnomad SAS exome

AF:

0.000474

Gnomad FIN exome

AF:

0.0000584

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000653

AC:

AN:

1164726

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

580054

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.000111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.000121

Gnomad4 NFE exome

AF:

0.00000783

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000196

AC:

AN:

61344

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

AN XY:

30078

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000346

Gnomad4 SAS

AF:

0.000446

Gnomad4 FIN

AF:

0.000262

Gnomad4 NFE

AF:

0.0000371

Gnomad4 OTH

AF:

0.00119

ExAC

AF:

0.000275

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

Jul 06, 2021

The c.323C>A (p.T108N) alteration is located in exon 1 (coding exon 1) of the KRTAP4-7 gene. This alteration results from a C to A substitution at nucleotide position 323, causing the threonine (T) at amino acid position 108 to be replaced by an asparagine (N). 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

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

DANN

Benign

0.94

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.022

.;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.013

Sift

Benign

0.037

D;.

Sift4G

Uncertain

0.051

T;T

Vest4

0.20

MutPred

0.36

Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);

MVP

0.048

MPC

0.037

ClinPred

0.0070

GERP RS

1.0

gMVP

0.097

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