chr6-169670627-A-C

Variant names:

• chr6-169670627-A-C
• rs4236176
• NM_182552.5:c.398T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182552.5(WDR27):​c.398T>G​(p.Leu133Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR27 NM_182552.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 44 publications found

Genes affected

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]

ENSG00000285733 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.147142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182552.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	NM_182552.5	MANE Select	c.398T>G	p.Leu133Arg	missense	Exon 4 of 26	NP_872358.4
	WDR27	NM_001350624.2		c.398T>G	p.Leu133Arg	missense	Exon 5 of 14	NP_001337553.1
	WDR27	NM_001350625.2		c.398T>G	p.Leu133Arg	missense	Exon 4 of 13	NP_001337554.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	ENST00000448612.6	TSL:1 MANE Select	c.398T>G	p.Leu133Arg	missense	Exon 4 of 26	ENSP00000416289.1
	WDR27	ENST00000423258.5	TSL:1	c.331+1628T>G		intron	N/A	ENSP00000397869.1
	ENSG00000285733	ENST00000648086.1		c.331+1628T>G		intron	N/A	ENSP00000497979.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461688 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.9
DANN	Benign	0.93
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.45
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.068
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0040	D
Vest4		0.35
MutPred		0.65		Loss of stability (P = 0.0187)
MVP		0.099
MPC		0.063
ClinPred		0.089	T
GERP RS		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.35
Mutation Taster		=98/2	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: rs4236176; hg19: chr6-170070723;