Variant chr17-41034721-C-G 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_030966.2(KRTAP1-3):c.101G>C(p.Cys34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,443,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP1-3
NM_030966.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

KRTAP1-3 (HGNC:16771): (keratin associated protein 1-3) 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 high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

KRTAP1-3 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=0.028674066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP1-3	NM_030966.2 linkuse as main transcript	c.101G>C	p.Cys34Ser	missense_variant	1/1	ENST00000344363.7	NP_112228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP1-3	ENST00000344363.7 linkuse as main transcript	c.101G>C	p.Cys34Ser	missense_variant	1/1		NM_030966.2	ENSP00000344420	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

147

AN:

142006

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00113

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.000586

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000700

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000840

AC:

197

AN:

234608

Hom.:

AF XY:

0.000723

AC XY:

AN XY:

128560

show subpopulations

Gnomad AFR exome

AF:

0.00282

Gnomad AMR exome

AF:

0.000575

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00118

Gnomad SAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.000485

Gnomad NFE exome

AF:

0.000955

Gnomad OTH exome

AF:

0.000862

GnomAD4 exome

AF:

0.000660

AC:

952

AN:

1443220

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

461

AN XY:

718466

show subpopulations

Gnomad4 AFR exome

AF:

0.000195

Gnomad4 AMR exome

AF:

0.000405

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000381

Gnomad4 NFE exome

AF:

0.000815

Gnomad4 OTH exome

AF:

0.000320

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00103

AC:

147

AN:

142120

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

69300

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00113

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.000586

Gnomad4 NFE

AF:

0.000700

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0117

Hom.:

ExAC

AF:

0.000407

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

Aug 03, 2022

The c.101G>C (p.C34S) alteration is located in exon 1 (coding exon 1) of the KRTAP1-3 gene. This alteration results from a G to C substitution at nucleotide position 101, causing the cysteine (C) at amino acid position 34 to be replaced by a serine (S). 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

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.88

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.0039

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.82

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0090

Vest4

0.36

MVP

0.082

MPC

0.29

ClinPred

0.068

GERP RS

1.5

gMVP

0.18

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