Genetic Variant NM_198285.3:c.1012C>T (chr7-151381701-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198285.3(WDR86):c.1012C>T(p.Arg338Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,489,306 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

WDR86
NM_198285.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.567

Publications

0 publications found

Variant links:

Genes affected

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

WDR86 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04706031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3 link	c.1012C>T	p.Arg338Cys	missense_variant	Exon 6 of 6	ENST00000334493.11	NP_938026.2	Q86TI4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR86	ENST00000334493.11 link	c.1012C>T	p.Arg338Cys	missense_variant	Exon 6 of 6	5	NM_198285.3	ENSP00000335522.7		Q86TI4-3

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000468

AC:

AN:

83410

AF XY:

0.000496

show subpopulations

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:

0.000766

Gnomad NFE exome

AF:

0.000976

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00107

AC:

1424

AN:

1337026

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

699

AN XY:

657988

show subpopulations

African (AFR)

AF:

0.000112

AC:

AN:

26790

American (AMR)

AF:

0.00

AC:

AN:

25006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21640

East Asian (EAS)

AF:

0.00

AC:

AN:

32798

South Asian (SAS)

AF:

0.0000423

AC:

AN:

70934

European-Finnish (FIN)

AF:

0.000690

AC:

AN:

42014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4070

European-Non Finnish (NFE)

AF:

0.00129

AC:

1368

AN:

1058618

Other (OTH)

AF:

0.000381

AC:

AN:

55156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

174

261

348

435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000486

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41574

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68008

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000685

Hom.:

Bravo

AF:

0.000484

ExAC

AF:

0.000128

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1012C>T (p.R338C) alteration is located in exon 6 (coding exon 6) of the WDR86 gene. This alteration results from a C to T substitution at nucleotide position 1012, causing the arginine (R) at amino acid position 338 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.43

PhyloP100

0.57

PROVEAN

Benign

-0.44

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Benign

0.43

Vest4

0.17

MVP

0.60

ClinPred

0.32

GERP RS

3.5

Varity_R

0.58

gMVP

0.16

Mutation Taster

=66/34

polymorphism

(source)

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

Publications

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NM_198285.3:c.1012C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over