chr17-41097890-A-ACAGCAGCTGGAGATGCAGCATCTGGGGTGG

Position:

• chr17-41097890-A-ACAGCAGCTGGAGATGCAGCATCTGGGGTGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_031960.3(KRTAP4-8):​c.194_195insCCACCCCAGATGCTGCATCTCCAGCTGCTG​(p.Cys65_Arg66insHisProArgCysCysIleSerSerCysCys) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 41,632 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (20 hom., cov: 26)
  • Exomes 𝑓: 0.00021 (14 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-8 NM_031960.3 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_031960.3.
• BP6: Variant 17-41097890-A-ACAGCAGCTGGAGATGCAGCATCTGGGGTGG is Benign according to our data. Variant chr17-41097890-A-ACAGCAGCTGGAGATGCAGCATCTGGGGTGG is described in ClinVar as [Likely_benign]. Clinvar id is 2647753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-8	NM_031960.3	c.194_195insCCACCCCAGATGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insHisProArgCysCysIleSerSerCysCys	disruptive_inframe_insertion	1/1	ENST00000333822.5	NP_114166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-8	ENST00000333822.5	c.194_195insCCACCCCAGATGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insHisProArgCysCysIleSerSerCysCys	disruptive_inframe_insertion	1/1	6	NM_031960.3	ENSP00000328444.4

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 84 AN: 41620 Hom.: 20 Cov.: 26

Gnomad AFR AF: 0.000274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000212

Gnomad ASJ AF: 0.00181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00249

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000289 AC: 15 AN: 51934 Hom.: 1 AF XY: 0.000320 AC XY: 9 AN XY: 28132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000491

Gnomad FIN exome AF: 0.000891

Gnomad NFE exome AF: 0.000307

Gnomad OTH exome AF: 0.000831

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000208 AC: 145 AN: 695562 Hom.: 14 Cov.: 104 AF XY: 0.000254 AC XY: 89 AN XY: 350444

Gnomad4 AFR exome AF: 0.0000791

Gnomad4 AMR exome AF: 0.0000485

Gnomad4 ASJ exome AF: 0.000143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00195

Gnomad4 NFE exome AF: 0.000155

Gnomad4 OTH exome AF: 0.0000956

GnomAD4 genome AF: 0.00202 AC: 84 AN: 41632 Hom.: 20 Cov.: 26 AF XY: 0.00231 AC XY: 47 AN XY: 20324

Gnomad4 AFR AF: 0.000273

Gnomad4 AMR AF: 0.000212

Gnomad4 ASJ AF: 0.00181

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.00249

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

KRTAP4-8: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs761473739; hg19: chr17-39254142;