6-169670627-A-G

Variant names:

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

Variant summary

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

The NM_182552.5(WDR27):​c.398T>C​(p.Leu133Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,534 control chromosomes in the GnomAD database, including 93,630 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.37 (12435 hom., cov: 32)
  • Exomes 𝑓: 0.30 (81195 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.5572293E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

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>C	p.Leu133Pro	missense	Exon 4 of 26	NP_872358.4
	WDR27	NM_001350624.2		c.398T>C	p.Leu133Pro	missense	Exon 5 of 14	NP_001337553.1
	WDR27	NM_001350625.2		c.398T>C	p.Leu133Pro	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>C	p.Leu133Pro	missense	Exon 4 of 26	ENSP00000416289.1
	WDR27	ENST00000423258.5	TSL:1	c.331+1628T>C		intron	N/A	ENSP00000397869.1
	ENSG00000285733	ENST00000648086.1		c.331+1628T>C		intron	N/A	ENSP00000497979.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56690 AN: 151854 Hom.: 12396 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.404 AC: 100615 AN: 249232 AF XY: 0.389

Gnomad AFR exome AF: 0.453

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.955

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.304 AC: 444602 AN: 1461562 Hom.: 81195 Cov.: 35 AF XY: 0.306 AC XY: 222214 AN XY: 727066

African (AFR) AF: 0.457 AC: 15311 AN: 33478

American (AMR) AF: 0.639 AC: 28555 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7896 AN: 26136

East Asian (EAS) AF: 0.923 AC: 36629 AN: 39700

South Asian (SAS) AF: 0.422 AC: 36347 AN: 86226

European-Finnish (FIN) AF: 0.278 AC: 14819 AN: 53400

Middle Eastern (MID) AF: 0.279 AC: 1608 AN: 5768

European-Non Finnish (NFE) AF: 0.254 AC: 282892 AN: 1111776

Other (OTH) AF: 0.340 AC: 20545 AN: 60364

GnomAD4 genome AF: 0.374 AC: 56777 AN: 151972 Hom.: 12435 Cov.: 32 AF XY: 0.381 AC XY: 28319 AN XY: 74294

African (AFR) AF: 0.455 AC: 18851 AN: 41406

American (AMR) AF: 0.510 AC: 7781 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3468

East Asian (EAS) AF: 0.937 AC: 4825 AN: 5150

South Asian (SAS) AF: 0.457 AC: 2197 AN: 4806

European-Finnish (FIN) AF: 0.272 AC: 2877 AN: 10588

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18143 AN: 67976

Other (OTH) AF: 0.373 AC: 785 AN: 2106

Alfa AF: 0.308 Hom.: 31906

Bravo AF: 0.398

TwinsUK AF: 0.251 AC: 929

ALSPAC AF: 0.257 AC: 991

ESP6500AA AF: 0.432 AC: 1677

ESP6500EA AF: 0.261 AC: 2170

ExAC AF: 0.395 AC: 47718

Asia WGS AF: 0.684 AC: 2376 AN: 3478

EpiCase AF: 0.271

EpiControl AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.13
DANN	Benign	0.031
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	8.6e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.8	N
PhyloP100		0.45
PrimateAI	Benign	0.28	T
PROVEAN	Benign	5.6	N
REVEL	Benign	0.054
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.064
MPC		0.025
ClinPred		0.00088	T
GERP RS		0.66
gMVP		0.31
Mutation Taster		=99/1	polymorphism (auto)

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; COSMIC: COSV61208256; COSMIC: COSV61208256;