chr9-113320484-C-T

Variant names:

• chr9-113320484-C-T
• rs141627600
• NM_001012361.4:c.653G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001012361.4(WDR31):​c.653G>A​(p.Arg218Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000486 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: WDR31 NM_001012361.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97
• Publications: 8 publications found

Genes affected

WDR31 (HGNC:21421): (WD repeat domain 31) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32672793).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012361.4. 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
	WDR31	NM_001012361.4	MANE Select	c.653G>A	p.Arg218Gln	missense	Exon 9 of 11	NP_001012361.1	Q8NA23-1
	WDR31	NM_145241.5		c.650G>A	p.Arg217Gln	missense	Exon 9 of 11	NP_660284.1	Q8NA23-2
	WDR31	NM_001006615.3		c.278G>A	p.Arg93Gln	missense	Exon 8 of 10	NP_001006616.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR31	ENST00000374193.9	TSL:1 MANE Select	c.653G>A	p.Arg218Gln	missense	Exon 9 of 11	ENSP00000363308.3	Q8NA23-1
	WDR31	ENST00000461942.5	TSL:1	n.842G>A		non_coding_transcript_exon	Exon 9 of 11
	WDR31	ENST00000944273.1		c.653G>A	p.Arg218Gln	missense	Exon 8 of 10	ENSP00000614332.1

Frequencies

GnomAD3 genomes AF: 0.000512 AC: 78 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000618 AC: 155 AN: 250822 AF XY: 0.000502

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000484 AC: 707 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.000479 AC XY: 348 AN XY: 727092

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.000403 AC: 18 AN: 44674

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86198

European-Finnish (FIN) AF: 0.000749 AC: 40 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000559 AC: 621 AN: 1111868

Other (OTH) AF: 0.000364 AC: 22 AN: 60386

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38 AN XY: 74494

African (AFR) AF: 0.0000241 AC: 1 AN: 41578

American (AMR) AF: 0.00111 AC: 17 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68042

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000594 Hom.: 0

Bravo AF: 0.000484

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000857 AC: 104

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00130

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	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0060	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.0
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.84
MVP		0.71
MPC		0.59
ClinPred		0.14	T
GERP RS		5.9
Varity_R		0.49
gMVP		0.45
Mutation Taster		=38/62	disease causing

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: rs141627600; hg19: chr9-116082764; COSMIC: COSV59147626; COSMIC: COSV59147626;