ENST00000497136.6:n.*3382A>T

Variant names:

• chr10-120909147-A-T
• rs12259815
• ENST00000497136.6:n.*3382A>T

Variant summary

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

The ENST00000497136.6(WDR11):​n.*3382A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 175,200 control chromosomes in the GnomAD database, including 756 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 0.054 (752 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (4 hom.)
• Consequence: WDR11 ENST00000497136.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 1 publications found

Genes affected

WDR11 (HGNC:13831): (WD repeat domain 11) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]

WDR11 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 14 with or without anosmia

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• intellectual developmental disorder, autosomal recessive 78

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105378519 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.*434A>T		3_prime_UTR_variant	Exon 29 of 29	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000497136.6	n.*3382A>T		non_coding_transcript_exon_variant	Exon 26 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.*2628A>T		non_coding_transcript_exon_variant	Exon 22 of 22	2		ENSP00000475076.1
WDR11	ENST00000263461.11	c.*434A>T		3_prime_UTR_variant	Exon 29 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000497136.6	n.*3382A>T		3_prime_UTR_variant	Exon 26 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.*2628A>T		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8191 AN: 152124 Hom.: 750 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.00449 AC: 103 AN: 22958 Hom.: 4 Cov.: 0 AF XY: 0.00434 AC XY: 52 AN XY: 11970

African (AFR) AF: 0.145 AC: 55 AN: 380

American (AMR) AF: 0.0131 AC: 38 AN: 2910

Ashkenazi Jewish (ASJ) AF: 0.00505 AC: 2 AN: 396

East Asian (EAS) AF: 0.00 AC: 0 AN: 1772

South Asian (SAS) AF: 0.00 AC: 0 AN: 2798

European-Finnish (FIN) AF: 0.000926 AC: 1 AN: 1080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 48

European-Non Finnish (NFE) AF: 0.000240 AC: 3 AN: 12522

Other (OTH) AF: 0.00380 AC: 4 AN: 1052

GnomAD4 genome AF: 0.0539 AC: 8204 AN: 152242 Hom.: 752 Cov.: 33 AF XY: 0.0523 AC XY: 3893 AN XY: 74458

African (AFR) AF: 0.186 AC: 7725 AN: 41512

American (AMR) AF: 0.0213 AC: 325 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68018

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.00261 Hom.: 5

Bravo AF: 0.0616

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.82
PhyloP100		-0.11
Mutation Taster		=100/0	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: rs12259815; hg19: chr10-122668659;