Genetic Variant KRTAP4-8:p.Cys65_Arg66insLeuProArgCysCysIleSerSerCysCys (chr17-41097890-A-ACAGCAGCTGGAGATGCAGCATCTGGGGAGG) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_031960.3(KRTAP4-8):c.194_195insCCTCCCCAGATGCTGCATCTCCAGCTGCTG(p.Cys65_Arg66insLeuProArgCysCysIleSerSerCysCys) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 41,640 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTAP4-8
NM_031960.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

KRTAP4-8 (HGNC:17230): (keratin associated protein 4-8) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP4-8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_031960.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-8	NM_031960.3 link	c.194_195insCCTCCCCAGATGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insLeuProArgCysCysIleSerSerCysCys	disruptive_inframe_insertion	Exon 1 of 1	ENST00000333822.5	NP_114166.1	Q9BYQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-8	ENST00000333822.5 link	c.194_195insCCTCCCCAGATGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insLeuProArgCysCysIleSerSerCysCys	disruptive_inframe_insertion	Exon 1 of 1	6	NM_031960.3	ENSP00000328444.4		Q9BYQ9

Frequencies

GnomAD3 genomes

AF:

0.0000480

AC:

AN:

41640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000956

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000216

AC:

AN:

695718

Hom.:

Cov.:

104

AF XY:

0.0000285

AC XY:

AN XY:

350540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000480

AC:

AN:

41640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000956

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over