7-135204389-G-T

Variant names:

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

Variant summary

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

The NM_014149.4(WDR91):​c.770C>A​(p.Pro257His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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>A	p.Pro257His	missense	Exon 6 of 15	NP_054868.3
	WDR91	NM_001362737.2		c.770C>A	p.Pro257His	missense	Exon 6 of 15	NP_001349666.1
	WDR91	NM_001362736.2		c.770C>A	p.Pro257His	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>A	p.Pro257His	missense	Exon 6 of 15	ENSP00000346466.4	A4D1P6-1
	WDR91	ENST00000423565.5	TSL:5	c.665C>A	p.Pro222His	missense	Exon 6 of 15	ENSP00000392555.1	C9J1X0
	WDR91	ENST00000956716.1		c.770C>A	p.Pro257His	missense	Exon 6 of 15	ENSP00000626775.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 131122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
PhyloP100		6.5
Varity_R		0.14
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs292592; hg19: chr7-134889141;