3-49171662-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5 BP4 BS2

The NM_173546.3(KLHDC8B):c.-158C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 152,510 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0047 (2 hom., cov: 33)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: KLHDC8B NM_173546.3 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.456

Genes affected

KLHDC8B (HGNC:28557): (kelch domain containing 8B) This gene encodes a protein which forms a distinct beta-propeller protein structure of kelch domains allowing for protein-protein interactions. Mutations in this gene have been associated with Hodgkin lymphoma. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PP5: Variant 3-49171662-C-T is Pathogenic according to our data. Variant chr3-49171662-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 273.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).. Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAd at 718 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHDC8B	NM_173546.3	c.-158C>T		5_prime_UTR_variant	1/6	ENST00000332780.4
KLHDC8B	XM_005264938.4	c.-158C>T		5_prime_UTR_variant	1/6
KLHDC8B	XM_006713015.4	c.-158C>T		5_prime_UTR_variant	1/6
KLHDC8B	XM_006713016.4	c.-158C>T		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHDC8B	ENST00000332780.4	c.-158C>T		5_prime_UTR_variant	1/6	1	NM_173546.3	P1
KLHDC8B	ENST00000459846.6	n.41C>T		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152248 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00807

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.0208 AC: 3 AN: 144 Hom.: 0 Cov.: 0 AF XY: 0.0273 AC XY: 3 AN XY: 110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0242

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00471 AC: 718 AN: 152366 Hom.: 2 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74504

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00461

Gnomad4 NFE AF: 0.00807

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00507 Hom.: 0

Bravo AF: 0.00446

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Classic Hodgkin lymphoma Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.9
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs387906223; hg19: chr3-49209095;