Genetic Variant NM_033187.2:c.285_286insCAGACCACCTGCTGC (chr17-41167887-T-TGCAGCAGGTGGTCTG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_033187.2(KRTAP4-3):c.285_286insCAGACCACCTGCTGC(p.Cys95_Arg96insGlnThrThrCysCys) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 130,666 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 10 hom., cov: 28)

Exomes 𝑓: 0.00013 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP4-3
NM_033187.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.275

Variant links:

Genes affected

KRTAP4-3 (HGNC:18908): (keratin associated protein 4-3) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP4-3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_033187.2.

BP6

Variant 17-41167887-T-TGCAGCAGGTGGTCTG is Benign according to our data. Variant chr17-41167887-T-TGCAGCAGGTGGTCTG is described in ClinVar as [Likely_benign]. Clinvar id is 3257581.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-3	NM_033187.2 link	c.285_286insCAGACCACCTGCTGC	p.Cys95_Arg96insGlnThrThrCysCys	conservative_inframe_insertion	Exon 1 of 1	ENST00000391356.4	NP_149443.1	Q9BYR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-3	ENST00000391356.4 link	c.285_286insCAGACCACCTGCTGC	p.Cys95_Arg96insGlnThrThrCysCys	conservative_inframe_insertion	Exon 1 of 1	6	NM_033187.2	ENSP00000375151.2		Q9BYR4

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

252

AN:

130612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00856

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000435

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:

0.0000156

Gnomad OTH

AF:

0.00274

GnomAD3 exomes

AF:

0.000140

AC:

AN:

142506

Hom.:

AF XY:

0.0000519

AC XY:

AN XY:

77126

show subpopulations

Gnomad AFR exome

AF:

0.00309

Gnomad AMR exome

AF:

0.000101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000129

AC:

184

AN:

1421946

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

703912

show subpopulations

Gnomad4 AFR exome

AF:

0.00412

Gnomad4 AMR exome

AF:

0.000659

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000732

Gnomad4 OTH exome

AF:

0.000288

GnomAD4 genome

AF:

0.00195

AC:

255

AN:

130666

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

126

AN XY:

63758

show subpopulations

Gnomad4 AFR

AF:

0.00865

Gnomad4 AMR

AF:

0.000435

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000156

Gnomad4 OTH

AF:

0.00271

Alfa

AF:

0.0294

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KRTAP4-3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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