7-151381740-C-A

Variant names:

• chr7-151381740-C-A
• rs370813546
• NM_198285.3:c.973G>T

Variant summary

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

The NM_198285.3(WDR86):​c.973G>T​(p.Gly325Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G325S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3	c.973G>T	p.Gly325Cys	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.973G>T	p.Gly325Cys	missense_variant	Exon 6 of 6	5	NM_198285.3	ENSP00000335522.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362098 Hom.: 0 Cov.: 53 AF XY: 0.00 AC XY: 0 AN XY: 669978

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29584

American (AMR) AF: 0.00 AC: 0 AN: 29770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22574

East Asian (EAS) AF: 0.00 AC: 0 AN: 34946

South Asian (SAS) AF: 0.00 AC: 0 AN: 74092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4854

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1064442

Other (OTH) AF: 0.00 AC: 0 AN: 56180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.
Eigen	Benign	0.044
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.70	T;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.81	T
PhyloP100		2.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.018	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.99	D;.
Vest4		0.17
MutPred		0.59		Loss of MoRF binding (P = 0.2525);.;
MVP		0.51
MPC		1.1
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.47
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs370813546; hg19: chr7-151078826;