chr17-41097890-A-ACAGCAGCTGGAGATGCAGCAGCTGGGGCGG

Variant names:

• chr17-41097890-A-ACAGCAGCTGGAGATGCAGCAGCTGGGGCGG
• rs761473739
• NM_031960.3:c.194_195insCCGCCCCAGCTGCTGCATCTCCAGCTGCTG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_031960.3(KRTAP4-8):​c.194_195insCCGCCCCAGCTGCTGCATCTCCAGCTGCTG​(p.Cys65_Arg66insArgProSerCysCysIleSerSerCysCys) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 41,636 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 0.00022 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00065 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-8 NM_031960.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• 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	c.194_195insCCGCCCCAGCTGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insArgProSerCysCysIleSerSerCysCys	disruptive_inframe_insertion	Exon 1 of 1	ENST00000333822.5	NP_114166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-8	ENST00000333822.5	c.194_195insCCGCCCCAGCTGCTGCATCTCCAGCTGCTG	p.Cys65_Arg66insArgProSerCysCysIleSerSerCysCys	disruptive_inframe_insertion	Exon 1 of 1	6	NM_031960.3	ENSP00000328444.4

Frequencies

GnomAD3 genomes AF: 0.000216 AC: 9 AN: 41624 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000439

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000335

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000963 AC: 5 AN: 51934 Hom.: 0 AF XY: 0.000107 AC XY: 3 AN XY: 28132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000280

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000154

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000649 AC: 451 AN: 694730 Hom.: 18 Cov.: 104 AF XY: 0.000697 AC XY: 244 AN XY: 349984

Gnomad4 AFR exome AF: 0.000713

Gnomad4 AMR exome AF: 0.000388

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.000208

Gnomad4 SAS exome AF: 0.00179

Gnomad4 FIN exome AF: 0.00124

Gnomad4 NFE exome AF: 0.000542

Gnomad4 OTH exome AF: 0.000670

GnomAD4 genome AF: 0.000216 AC: 9 AN: 41636 Hom.: 0 Cov.: 26 AF XY: 0.000246 AC XY: 5 AN XY: 20330

Gnomad4 AFR AF: 0.000137

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000440

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000335

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;