22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG

Position:

• chr22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_138433.5(KLHDC7B):​c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC​(p.Ala562_Leu563insProThrProAlaAlaSerProAlaLeuThrProValProThrProAlaLeuSerProAlaProThrProAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (9 hom., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: KLHDC7B NM_138433.5 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.356

Genes affected

KLHDC7B (HGNC:25145): (kelch domain containing 7B)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_138433.5
• BP6: Variant 22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG is Benign according to our data. Variant chr22-50547870-C-CCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCCCAACCCCAGCCG is described in ClinVar as [Likely_benign]. Clinvar id is 2653402.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5	c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC	p.Ala562_Leu563insProThrProAlaAlaSerProAlaLeuThrProValProThrProAlaLeuSerProAlaProThrProAla	disruptive_inframe_insertion	1/1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3	c.1687_1688insCAACCCCAGCCGCATCCCCAGCCCTAACCCCAGTCCCAACCCCAGCCCTAAGCCCAGCTCCAACTCCAGCCC	p.Ala562_Leu563insProThrProAlaAlaSerProAlaLeuThrProValProThrProAlaLeuSerProAlaProThrProAla	disruptive_inframe_insertion	1/1		NM_138433.5	ENSP00000497256.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 22 AN: 124636 Hom.: 9 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0000300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000744

Gnomad SAS AF: 0.000520

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000176 AC: 22 AN: 124710 Hom.: 9 Cov.: 23 AF XY: 0.000232 AC XY: 14 AN XY: 60224

Gnomad4 AFR AF: 0.0000299

Gnomad4 AMR AF: 0.000340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000746

Gnomad4 SAS AF: 0.000522

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000207

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

Jan 01, 2023

KLHDC7B: 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: rs2069749252; hg19: chr22-50986299;