17-41034702-G-GCAGCAGCTTGGCTGGCAGCAGCTGGTCTCA

Position:

• chr17-41034702-G-GCAGCAGCTTGGCTGGCAGCAGCTGGTCTCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_030966.2(KRTAP1-3):​c.119_120insTGAGACCAGCTGCTGCCAGCCAAGCTGCTG​(p.Glu31_Cys40dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 100,286 control chromosomes in the GnomAD database, including 5,771 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5771 hom., cov: 32)
  • Exomes 𝑓: 0.12 (33033 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP1-3 NM_030966.2 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.358

Genes affected

KRTAP1-3 (HGNC:16771): (keratin associated protein 1-3) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_030966.2.
• BP6: Variant 17-41034702-G-GCAGCAGCTTGGCTGGCAGCAGCTGGTCTCA is Benign according to our data. Variant chr17-41034702-G-GCAGCAGCTTGGCTGGCAGCAGCTGGTCTCA is described in ClinVar as [Benign]. Clinvar id is 768881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP1-3	NM_030966.2	c.119_120insTGAGACCAGCTGCTGCCAGCCAAGCTGCTG	p.Glu31_Cys40dup	inframe_insertion	1/1	ENST00000344363.7	NP_112228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP1-3	ENST00000344363.7	c.119_120insTGAGACCAGCTGCTGCCAGCCAAGCTGCTG	p.Glu31_Cys40dup	inframe_insertion	1/1		NM_030966.2	ENSP00000344420	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 26037 AN: 100226 Hom.: 5758 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.120 AC: 154697 AN: 1289298 Hom.: 33033 Cov.: 36 AF XY: 0.129 AC XY: 83388 AN XY: 644352

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.0914

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.260 AC: 26073 AN: 100286 Hom.: 5771 Cov.: 32 AF XY: 0.252 AC XY: 12200 AN XY: 48452

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.251

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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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: rs1046579147; hg19: chr17-39190954;