7-151381979-A-T

Variant names:

• chr7-151381979-A-T
• NM_198285.3:c.865T>A

Variant summary

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

The NM_198285.3(WDR86):​c.865T>A​(p.Phe289Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000484 in 1,446,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• 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 (REVEL=0.251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3	c.865T>A	p.Phe289Ile	missense_variant, splice_region_variant	Exon 5 of 6	ENST00000334493.11	NP_938026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR86	ENST00000334493.11	c.865T>A	p.Phe289Ile	missense_variant, splice_region_variant	Exon 5 of 6	5	NM_198285.3	ENSP00000335522.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1446692 Hom.: 0 Cov.: 34 AF XY: 0.00000418 AC XY: 3 AN XY: 718416

African (AFR) AF: 0.00 AC: 0 AN: 33214

American (AMR) AF: 0.00 AC: 0 AN: 42686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25852

East Asian (EAS) AF: 0.00 AC: 0 AN: 38914

South Asian (SAS) AF: 0.00 AC: 0 AN: 84078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1105630

Other (OTH) AF: 0.0000167 AC: 1 AN: 59768

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.865T>A (p.F289I) alteration is located in exon 5 (coding exon 5) of the WDR86 gene. This alteration results from a T to A substitution at nucleotide position 865, causing the phenylalanine (F) at amino acid position 289 to be replaced by an isoleucine (I). 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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.64	D
PhyloP100		5.1
Vest4		0.31
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.15
Mutation Taster		=35/165	disease causing (fs/PTC)

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

hg19: chr7-151079065;