rs1433656318

Variant names:

• chr3-49173019-G-A
• rs1433656318
• NM_173546.3:c.250G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-49173019-G-A
• chr3-49173019-G-C
• chr3-49173019-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173546.3(KLHDC8B):​c.250G>A​(p.Val84Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)
• Consequence: KLHDC8B NM_173546.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4135126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC8B	NM_173546.3	c.250G>A	p.Val84Met	missense_variant	Exon 2 of 6	ENST00000332780.4	NP_775817.1
KLHDC8B	XM_006713015.4	c.250G>A	p.Val84Met	missense_variant	Exon 2 of 6		XP_006713078.1
KLHDC8B	XM_006713016.4	c.250G>A	p.Val84Met	missense_variant	Exon 2 of 6		XP_006713079.1
KLHDC8B	XM_005264938.4	c.250G>A	p.Val84Met	missense_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.250G>A	p.Val84Met	missense_variant	Exon 2 of 6	1	NM_173546.3	ENSP00000327468.2
KLHDC8B	ENST00000476495.2	n.307G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
KLHDC8B	ENST00000459846.6	n.230+218G>A		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248144 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134484

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.079
Sift	Benign	0.080	T
Sift4G	Benign	0.13	T
Polyphen		0.24	B
Vest4		0.32
MutPred		0.55		Loss of catalytic residue at V84 (P = 0.0376);
MVP		0.73
MPC		0.45
ClinPred		0.24	T
GERP RS		3.3
Varity_R		0.054
gMVP		0.55

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: rs1433656318; hg19: chr3-49210452;