NM_198285.3:c.1012C>A

Variant names:

• chr7-151381701-G-T
• rs148787983
• NM_198285.3:c.1012C>A

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.1012C>A​(p.Arg338Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,337,026 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. R338C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567
• 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=0.22862986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3	c.1012C>A	p.Arg338Ser	missense_variant	Exon 6 of 6	ENST00000334493.11	NP_938026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR86	ENST00000334493.11	c.1012C>A	p.Arg338Ser	missense_variant	Exon 6 of 6	5	NM_198285.3	ENSP00000335522.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.48e-7 AC: 1 AN: 1337026 Hom.: 0 Cov.: 52 AF XY: 0.00000152 AC XY: 1 AN XY: 657988

African (AFR) AF: 0.00 AC: 0 AN: 26790

American (AMR) AF: 0.00 AC: 0 AN: 25006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21640

East Asian (EAS) AF: 0.00 AC: 0 AN: 32798

South Asian (SAS) AF: 0.00 AC: 0 AN: 70934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058618

Other (OTH) AF: 0.0000181 AC: 1 AN: 55156

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.45	T
PhyloP100		0.57
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.89	T
Vest4		0.22
MutPred		0.27		Gain of sheet (P = 0.0016);
MVP		0.60
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.58
gMVP		0.28
Mutation Taster		=51/149	disease causing

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: rs148787983; hg19: chr7-151078787;