Genetic Variant KRTAP4-12:p.Arg47Arg (chr17-41123982-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_031854.3(KRTAP4-12):c.141G>A(p.Arg47Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,256,976 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00040 ( 74 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP4-12
NM_031854.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.667

Variant links:

Genes affected

KRTAP4-12 (HGNC:16776): (keratin associated protein 4-12) 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, Jul 2008]

KRTAP4-12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-41123982-C-T is Benign according to our data. Variant chr17-41123982-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3898109.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.667 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-12	NM_031854.3 link	c.141G>A	p.Arg47Arg	synonymous_variant	Exon 1 of 1	ENST00000394014.2	NP_114060.1	Q9BQ66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-12	ENST00000394014.2 link	c.141G>A	p.Arg47Arg	synonymous_variant	Exon 1 of 1	6	NM_031854.3	ENSP00000377582.1		Q9BQ66

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

78148

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00300

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000632

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000437

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.000187

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00159

AC:

296

AN:

186532

Hom.:

120

AF XY:

0.000993

AC XY:

104

AN XY:

104682

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.000621

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000102

Gnomad SAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.000100

Gnomad NFE exome

AF:

0.0000323

Gnomad OTH exome

AF:

0.000486

GnomAD4 exome

AF:

0.000399

AC:

502

AN:

1256976

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

252

AN XY:

623814

show subpopulations

Gnomad4 AFR exome

AF:

0.00978

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.000448

Gnomad4 EAS exome

AF:

0.00143

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.000309

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.000420

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000588

AC:

AN:

78168

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

AN XY:

38564

show subpopulations

Gnomad4 AFR

AF:

0.00300

Gnomad4 AMR

AF:

0.000631

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000437

Gnomad4 SAS

AF:

0.000747

Gnomad4 FIN

AF:

0.000187

Gnomad4 NFE

AF:

0.000153

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00469

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KRTAP4-12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.90

DANN

Benign

0.65

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