3-49172830-C-A

Variant names:

• chr3-49172830-C-A
• NM_173546.3:c.61C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_173546.3(KLHDC8B):​c.61C>A​(p.Arg21Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KLHDC8B NM_173546.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC8B	NM_173546.3	c.61C>A	p.Arg21Arg	synonymous_variant	Exon 2 of 6	ENST00000332780.4	NP_775817.1
KLHDC8B	XM_006713015.4	c.61C>A	p.Arg21Arg	synonymous_variant	Exon 2 of 6		XP_006713078.1
KLHDC8B	XM_006713016.4	c.61C>A	p.Arg21Arg	synonymous_variant	Exon 2 of 6		XP_006713079.1
KLHDC8B	XM_005264938.4	c.61C>A	p.Arg21Arg	synonymous_variant	Exon 2 of 6		XP_005264995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC8B	ENST00000332780.4	c.61C>A	p.Arg21Arg	synonymous_variant	Exon 2 of 6	1	NM_173546.3	ENSP00000327468.2
KLHDC8B	ENST00000476495.2	n.118C>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
KLHDC8B	ENST00000459846.6	n.230+29C>A		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ 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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	15
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49210263;