rs775044801

Variant names:

• chr3-49172933-C-G
• rs775044801
• NM_173546.3:c.164C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-49172933-C-G
• chr3-49172933-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173546.3(KLHDC8B):​c.164C>G​(p.Ala55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: KLHDC8B NM_173546.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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 (MetaRNN=0.17828822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC8B	NM_173546.3	c.164C>G	p.Ala55Gly	missense_variant	Exon 2 of 6	ENST00000332780.4	NP_775817.1
KLHDC8B	XM_006713015.4	c.164C>G	p.Ala55Gly	missense_variant	Exon 2 of 6		XP_006713078.1
KLHDC8B	XM_006713016.4	c.164C>G	p.Ala55Gly	missense_variant	Exon 2 of 6		XP_006713079.1
KLHDC8B	XM_005264938.4	c.164C>G	p.Ala55Gly	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.164C>G	p.Ala55Gly	missense_variant	Exon 2 of 6	1	NM_173546.3	ENSP00000327468.2
KLHDC8B	ENST00000476495.2	n.221C>G		non_coding_transcript_exon_variant	Exon 1 of 3	2
KLHDC8B	ENST00000459846.6	n.230+132C>G		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.015
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.050
Sift	Benign	0.097	T
Sift4G	Benign	0.17	T
Polyphen		0.54	P
Vest4		0.10
MutPred		0.40		Loss of stability (P = 0.0567);
MVP		0.56
MPC		0.55
ClinPred		0.68	D
GERP RS		3.5
Varity_R		0.091
gMVP		0.20

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: rs775044801; hg19: chr3-49210366;