NM_198285.3:c.785C>T

Variant names:

• chr7-151385165-G-A
• rs781464544
• NM_198285.3:c.785C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198285.3(WDR86):​c.785C>T​(p.Ala262Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08154279).

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.785C>T	p.Ala262Val	missense	Exon 4 of 6	NP_938026.2	Q86TI4-3
	WDR86	NM_001284262.2		c.401C>T	p.Ala134Val	missense	Exon 4 of 6	NP_001271191.1	A0A0C4DGX6
	WDR86	NM_001284260.2		c.849C>T	p.Gly283Gly	synonymous	Exon 4 of 6	NP_001271189.1	Q86TI4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR86	ENST00000334493.11	TSL:5 MANE Select	c.785C>T	p.Ala262Val	missense	Exon 4 of 6	ENSP00000335522.7	Q86TI4-3
	WDR86	ENST00000621812.2	TSL:5	c.401C>T	p.Ala134Val	missense	Exon 4 of 6	ENSP00000482209.1	A0A0C4DGX6
	WDR86	ENST00000469830.2	TSL:2	c.849C>T	p.Gly283Gly	synonymous	Exon 4 of 6	ENSP00000419162.2	Q86TI4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 248190 AF XY: 0.00000742

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460756 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726714

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111852

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

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

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	Benign	0.093
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.056
Sift	Benign	0.71	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.19
MutPred		0.38		Loss of ubiquitination at K258 (P = 0.1264)
MVP		0.095
MPC		0.37
ClinPred		0.064	T
GERP RS		4.1
Varity_R		0.039
Mutation Taster		=89/11	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: rs781464544; hg19: chr7-151082251;