NM_014149.4:c.770C>T

Variant names:

• chr7-135204389-G-A
• rs292592
• NM_014149.4:c.770C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014149.4(WDR91):​c.770C>T​(p.Pro257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.721 in 1,613,788 control chromosomes in the GnomAD database, including 422,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (35855 hom., cov: 32)
  • Exomes 𝑓: 0.73 (386572 hom.)
• Consequence: WDR91 NM_014149.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• Publications: 46 publications found

Genes affected

WDR91 (HGNC:24997): (WD repeat domain 91) Enables phosphatidylinositol 3-kinase regulator activity. Involved in early endosome to late endosome transport; regulation of cellular protein catabolic process; and regulation of phosphatidylinositol 3-kinase activity. Located in cytosol; early endosome membrane; and late endosome membrane. Is extrinsic component of endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000231794 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1990732E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014149.4. 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
	WDR91	NM_014149.4	MANE Select	c.770C>T	p.Pro257Leu	missense	Exon 6 of 15	NP_054868.3
	WDR91	NM_001362737.2		c.770C>T	p.Pro257Leu	missense	Exon 6 of 15	NP_001349666.1
	WDR91	NM_001362736.2		c.770C>T	p.Pro257Leu	missense	Exon 6 of 16	NP_001349665.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR91	ENST00000354475.5	TSL:1 MANE Select	c.770C>T	p.Pro257Leu	missense	Exon 6 of 15	ENSP00000346466.4	A4D1P6-1
	WDR91	ENST00000423565.5	TSL:5	c.665C>T	p.Pro222Leu	missense	Exon 6 of 15	ENSP00000392555.1	C9J1X0
	WDR91	ENST00000956716.1		c.770C>T	p.Pro257Leu	missense	Exon 6 of 15	ENSP00000626775.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103323 AN: 151950 Hom.: 35836 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.728

GnomAD2 exomes AF: 0.720 AC: 180594 AN: 250966 AF XY: 0.722

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.724

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.726 AC: 1060762 AN: 1461720 Hom.: 386572 Cov.: 58 AF XY: 0.727 AC XY: 528299 AN XY: 727164

African (AFR) AF: 0.523 AC: 17495 AN: 33478

American (AMR) AF: 0.820 AC: 36679 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 19116 AN: 26134

East Asian (EAS) AF: 0.598 AC: 23735 AN: 39692

South Asian (SAS) AF: 0.738 AC: 63651 AN: 86238

European-Finnish (FIN) AF: 0.728 AC: 38873 AN: 53392

Middle Eastern (MID) AF: 0.713 AC: 4113 AN: 5768

European-Non Finnish (NFE) AF: 0.732 AC: 813813 AN: 1111920

Other (OTH) AF: 0.717 AC: 43287 AN: 60388

GnomAD4 genome AF: 0.680 AC: 103389 AN: 152068 Hom.: 35855 Cov.: 32 AF XY: 0.681 AC XY: 50589 AN XY: 74328

African (AFR) AF: 0.534 AC: 22155 AN: 41464

American (AMR) AF: 0.793 AC: 12118 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3049 AN: 5152

South Asian (SAS) AF: 0.737 AC: 3556 AN: 4824

European-Finnish (FIN) AF: 0.734 AC: 7765 AN: 10580

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.731 AC: 49696 AN: 67986

Other (OTH) AF: 0.730 AC: 1535 AN: 2104

Alfa AF: 0.714 Hom.: 131122

Bravo AF: 0.678

TwinsUK AF: 0.744 AC: 2760

ALSPAC AF: 0.727 AC: 2803

ESP6500AA AF: 0.550 AC: 2423

ESP6500EA AF: 0.724 AC: 6223

ExAC AF: 0.713 AC: 86547

Asia WGS AF: 0.690 AC: 2397 AN: 3478

EpiCase AF: 0.729

EpiControl AF: 0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.15
Sift	Benign	0.23	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.90	P
Vest4		0.12
MPC		0.57
ClinPred		0.014	T
GERP RS		5.4
Varity_R		0.14
gMVP		0.17
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs292592; hg19: chr7-134889141; COSMIC: COSV60371347; COSMIC: COSV60371347;