Genetic Variant KRTAP4-8:p.Cys65_Arg66insArgThrArgCysCysIleSerSerCysCys (chr17-41097890-A-ACAGCAGCTGGAGATGCAGCATCTGGTGCGG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_031960.3(KRTAP4-8):c.194_195insCCGCACCAGATGCTGCATCTCCAGCTGCTG(p.Cys65_Arg66insArgThrArgCysCysIleSerSerCysCys) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 41,638 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000024 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0 ( 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

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_031960.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031960.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-8	NM_031960.3	MANE Select	c.194_195insCCGCACCAGATGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insArgThrArgCysCysIleSerSerCysCys	disruptive_inframe_insertion	Exon 1 of 1	NP_114166.1	Q9BYQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-8	ENST00000333822.5	TSL:6 MANE Select	c.194_195insCCGCACCAGATGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insArgThrArgCysCysIleSerSerCysCys	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes

AF:

0.0000240

AC:

AN:

41638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000212

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

695720

Hom.:

Cov.:

104

AF XY:

0.00

AC XY:

AN XY:

350542

African (AFR)

AF:

0.00

AC:

AN:

12636

American (AMR)

AF:

0.00

AC:

AN:

20628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13948

East Asian (EAS)

AF:

0.00

AC:

AN:

28912

South Asian (SAS)

AF:

0.00

AC:

AN:

48904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26676

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

510306

Other (OTH)

AF:

0.00

AC:

AN:

31398

GnomAD4 genome

AF:

0.0000240

AC:

AN:

41638

Hom.:

Cov.:

AF XY:

0.0000492

AC XY:

AN XY:

20322

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

7298

American (AMR)

AF:

0.000212

AC:

AN:

4708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1108

East Asian (EAS)

AF:

0.00

AC:

AN:

2278

South Asian (SAS)

AF:

0.00

AC:

AN:

1752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

20910

Other (OTH)

AF:

0.00

AC:

AN:

570

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over