7-151381746-C-G

Variant names:

• chr7-151381746-C-G
• NM_198285.3:c.967G>C
• WDR86 p.Val323Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198285.3(WDR86):​c.967G>C​(p.Val323Leu) variant causes a missense, splice region 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. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V323M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: WDR86 NM_198285.3 missense, splice_region
• Scores: Splicing: ADA: 0.9899
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

WDR86 (HGNC:28020): (WD repeat domain 86)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198285.3. 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
	WDR86	NM_198285.3	MANE Select	c.967G>C	p.Val323Leu	missense splice_region	Exon 6 of 6	NP_938026.2	Q86TI4-3
	WDR86	NM_001284260.2		c.1031G>C	p.Gly344Ala	missense splice_region	Exon 6 of 6	NP_001271189.1	Q86TI4-4
	WDR86	NM_001284261.2		c.447G>C	p.Arg149Ser	missense splice_region	Exon 5 of 5	NP_001271190.1	Q86TI4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR86	ENST00000334493.11	TSL:5 MANE Select	c.967G>C	p.Val323Leu	missense splice_region	Exon 6 of 6	ENSP00000335522.7	Q86TI4-3
	WDR86	ENST00000469830.2	TSL:2	c.1031G>C	p.Gly344Ala	missense splice_region	Exon 6 of 6	ENSP00000419162.2	Q86TI4-4
	WDR86	ENST00000477459.5	TSL:2	c.447G>C	p.Arg149Ser	missense splice_region	Exon 5 of 5	ENSP00000417512.1	Q86TI4-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	0.99
Eigen	Benign	-0.066
Eigen_PC	Benign	0.019
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.8
PROVEAN	Benign	0.19	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
Varity_R		0.16
gMVP		0.18
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.89
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-151078832;