3-122414824-T-G

Variant names:

• chr3-122414824-T-G
• rs375158653
• NM_019069.4:c.705A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019069.4(WDR5B):​c.705A>C​(p.Lys235Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR5B NM_019069.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 0 publications found

Genes affected

WDR5B (HGNC:17826): (WD repeat domain 5B) This intronless gene encodes a protein containing several WD40 repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, including a trp-asp at the C-terminal end. The encoded protein may mediate protein-protein interactions. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31710464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR5B	NM_019069.4	c.705A>C	p.Lys235Asn	missense_variant	Exon 1 of 1	ENST00000330689.6	NP_061942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR5B	ENST00000330689.6	c.705A>C	p.Lys235Asn	missense_variant	Exon 1 of 1	6	NM_019069.4	ENSP00000330381.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.084
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.049
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.31
Sift	Benign	0.043	D
Sift4G	Uncertain	0.035	D
Polyphen		0.47	P
Vest4		0.27
MutPred		0.79		Loss of ubiquitination at K235 (P = 0.0309);
MVP		0.80
MPC		0.099
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.44
gMVP		0.74
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs375158653; hg19: chr3-122133671;