7-151385181-C-A

Variant names:

• chr7-151385181-C-A
• rs749672613
• NM_198285.3:c.769G>T

Variant summary

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

The NM_198285.3(WDR86):​c.769G>T​(p.Val257Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,594 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V257I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12
• Publications: 0 publications found

Genes affected

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

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=0.32840902).

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.769G>T	p.Val257Phe	missense	Exon 4 of 6	NP_938026.2	Q86TI4-3
	WDR86	NM_001284260.2		c.833G>T	p.Arg278Leu	missense	Exon 4 of 6	NP_001271189.1	Q86TI4-4
	WDR86	NM_001284262.2		c.385G>T	p.Val129Phe	missense	Exon 4 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.769G>T	p.Val257Phe	missense	Exon 4 of 6	ENSP00000335522.7	Q86TI4-3
	WDR86	ENST00000469830.2	TSL:2	c.833G>T	p.Arg278Leu	missense	Exon 4 of 6	ENSP00000419162.2	Q86TI4-4
	WDR86	ENST00000621812.2	TSL:5	c.385G>T	p.Val129Phe	missense	Exon 4 of 6	ENSP00000482209.1	A0A0C4DGX6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726604

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111848

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.39	T
PhyloP100		4.1
PROVEAN	Benign	0.83	N
REVEL	Benign	0.13
Sift	Benign	0.57	T
Sift4G	Benign	0.21	T
Vest4		0.28
MutPred		0.48		Loss of MoRF binding (P = 0.0496)
MVP		0.55
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.39
gMVP		0.41
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs749672613; hg19: chr7-151082267;