NM_019069.4:c.169G>A

Variant names:

• chr3-122415360-C-T
• NM_019069.4:c.169G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019069.4(WDR5B):​c.169G>A​(p.Ala57Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR5B NM_019069.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43
• 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]

WDR5B-DT (HGNC:55192): (WDR5B divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019069.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR5B	NM_019069.4	MANE Select	c.169G>A	p.Ala57Thr	missense	Exon 1 of 1	NP_061942.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR5B	ENST00000330689.6	TSL:6 MANE Select	c.169G>A	p.Ala57Thr	missense	Exon 1 of 1	ENSP00000330381.4	Q86VZ2
	WDR5B	ENST00000920957.1		c.169G>A	p.Ala57Thr	missense	Exon 2 of 2	ENSP00000591016.1
	WDR5B-DT	ENST00000686885.2		n.-160C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.098	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.4
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.62
Sift	Benign	0.061	T
Sift4G	Uncertain	0.045	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.82		Gain of disorder (P = 0.184)
MVP		0.89
MPC		0.37
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.61
gMVP		0.67
Mutation Taster		=48/52	disease causing

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

hg19: chr3-122134207;