rs41265373

Variant names:

• chr6-169602295-G-A
• rs41265373
• ENST00000648086.1:c.358C>T

Variant summary

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

The ENST00000648086.1(ENSG00000285733):​c.358C>T​(p.Gln120*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,561,958 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 (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: ENSG00000285733 ENST00000648086.1 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

Genes affected

ENSG00000285733 (HGNC:):

WDR27 (HGNC:21248): (WD repeat domain 27) This gene encodes a protein with multiple WD repeats. Proteins with these repeats may form scaffolds for protein-protein interaction and play key roles in cell signalling. Alternative splicing results in multiple transcript variants, but the full-length structure of some of these variants cannot be determined. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648086.1. 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
	WDR27	NM_182552.5	MANE Select	c.2348C>T	p.Pro783Leu	missense	Exon 23 of 26	NP_872358.4
	WDR27	NM_001202550.2		c.1967C>T	p.Pro656Leu	missense	Exon 20 of 22	NP_001189479.1	A2RRH5-2
	WDR27	NM_001350623.2		c.1775C>T	p.Pro592Leu	missense	Exon 18 of 21	NP_001337552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285733	ENST00000648086.1		c.358C>T	p.Gln120*	stop_gained	Exon 4 of 8	ENSP00000497979.1	A0A3B3ITY5
	WDR27	ENST00000448612.6	TSL:1 MANE Select	c.2348C>T	p.Pro783Leu	missense	Exon 23 of 26	ENSP00000416289.1	A2RRH5-4
	WDR27	ENST00000423258.5	TSL:1	c.1967C>T	p.Pro656Leu	missense	Exon 20 of 22	ENSP00000397869.1	A2RRH5-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000392 AC: 7 AN: 178390 AF XY: 0.0000635

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000944

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000560 AC: 79 AN: 1409634 Hom.: 0 Cov.: 30 AF XY: 0.0000589 AC XY: 41 AN XY: 696044

African (AFR) AF: 0.0000310 AC: 1 AN: 32264

American (AMR) AF: 0.00 AC: 0 AN: 37670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.00 AC: 0 AN: 36958

South Asian (SAS) AF: 0.00 AC: 0 AN: 79702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50150

Middle Eastern (MID) AF: 0.000701 AC: 4 AN: 5706

European-Non Finnish (NFE) AF: 0.0000664 AC: 72 AN: 1083572

Other (OTH) AF: 0.0000343 AC: 2 AN: 58374

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

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

Alfa AF: 0.0000785 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000255 AC: 3

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	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.4
DANN	Benign	0.54
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.045
Sift	Benign	0.56	T
Sift4G	Benign	0.14	T
Polyphen		0.0080	B
Vest4		0.28
MVP		0.061
MPC		0.022
ClinPred		0.032	T
GERP RS		2.8
gMVP		0.12
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs41265373; hg19: chr6-170002391;