7-151381746-C-T

Variant names:

• chr7-151381746-C-T
• rs1372416595
• NM_198285.3:c.967G>A

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>A​(p.Val323Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000528 in 1,513,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense, splice_region
• Scores: Splicing: ADA: 0.9895
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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>A	p.Val323Met	missense splice_region	Exon 6 of 6	NP_938026.2	Q86TI4-3
	WDR86	NM_001284260.2		c.1031G>A	p.Gly344Asp	missense splice_region	Exon 6 of 6	NP_001271189.1	Q86TI4-4
	WDR86	NM_001284262.2		c.583G>A	p.Val195Met	missense splice_region	Exon 6 of 6	NP_001271191.1	A0A0C4DGX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR86	ENST00000334493.11	TSL:5 MANE Select	c.967G>A	p.Val323Met	missense splice_region	Exon 6 of 6	ENSP00000335522.7	Q86TI4-3
	WDR86	ENST00000469830.2	TSL:2	c.1031G>A	p.Gly344Asp	missense splice_region	Exon 6 of 6	ENSP00000419162.2	Q86TI4-4
	WDR86	ENST00000621812.2	TSL:5	c.583G>A	p.Val195Met	missense splice_region	Exon 6 of 6	ENSP00000482209.1	A0A0C4DGX6

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152100 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000931 AC: 1 AN: 107406 AF XY: 0.0000172

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000367 AC: 5 AN: 1361870 Hom.: 0 Cov.: 51 AF XY: 0.00000448 AC XY: 3 AN XY: 669744

African (AFR) AF: 0.00 AC: 0 AN: 29624

American (AMR) AF: 0.00 AC: 0 AN: 29822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22540

East Asian (EAS) AF: 0.00 AC: 0 AN: 34954

South Asian (SAS) AF: 0.00 AC: 0 AN: 73972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4968

European-Non Finnish (NFE) AF: 0.00000470 AC: 5 AN: 1064024

Other (OTH) AF: 0.00 AC: 0 AN: 56134

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152100 Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

African (AFR) AF: 0.0000483 AC: 2 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000698 Hom.: 0

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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Benign	0.099
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.8
PROVEAN	Benign	0.030	N
REVEL	Benign	0.061
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Vest4		0.27
MutPred		0.25		Loss of MoRF binding (P = 0.0537)
MVP		0.60
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.099
gMVP		0.22
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.78
SpliceAI score (max)		0.010		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: rs1372416595; hg19: chr7-151078832;