Genetic Variant NM_024102.4:c.*1248A>T (chr1-111439982-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024102.4(WDR77):c.*1248A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,616 control chromosomes in the GnomAD database, including 3,701 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 0.20 ( 3684 hom., cov: 32)

Exomes 𝑓: 0.30 ( 17 hom. )

Consequence

WDR77
NM_024102.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0550

Publications

7 publications found

Variant links:

Genes affected

WDR77 (HGNC:29652): (WD repeat domain 77) The protein encoded by this gene is an androgen receptor coactivator that forms a complex with protein arginine methyltransferase 5, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins. The encoded protein may be involved in the early stages of prostate cancer, with most of the protein being nuclear-localized in benign cells but cytoplasmic in cancer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

WDR77 links:

ENSG00000243960 (HGNC:):

ENSG00000243960 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR77	NM_024102.4	MANE Select	c.*1248A>T	3_prime_UTR	Exon 10 of 10	NP_077007.1	Q9BQA1-1
WDR77	NM_001317062.2		c.*1248A>T	3_prime_UTR	Exon 10 of 10	NP_001303991.1
WDR77	NM_001317063.2		c.*1248A>T	3_prime_UTR	Exon 10 of 10	NP_001303992.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR77	ENST00000235090.10	TSL:1 MANE Select	c.*1248A>T	3_prime_UTR	Exon 10 of 10	ENSP00000235090.5	Q9BQA1-1
ENSG00000243960	ENST00000416099.1	TSL:2	n.537+710A>T	intron	N/A
ENSG00000243960	ENST00000445680.1	TSL:3	n.227+1156A>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30500

AN:

152066

Hom.:

3684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.301

AC:

130

AN:

432

Hom.:

Cov.:

AF XY:

0.286

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.304

AC:

129

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.200

AC:

30502

AN:

152184

Hom.:

3684

Cov.:

AF XY:

0.202

AC XY:

15023

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0837

AC:

3474

AN:

41530

American (AMR)

AF:

0.152

AC:

2325

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

506

AN:

3468

East Asian (EAS)

AF:

0.130

AC:

673

AN:

5188

South Asian (SAS)

AF:

0.236

AC:

1137

AN:

4822

European-Finnish (FIN)

AF:

0.276

AC:

2917

AN:

10580

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18757

AN:

67986

Other (OTH)

AF:

0.186

AC:

393

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1203

2405

3608

4810

6013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.153

Hom.:

340

Bravo

AF:

0.181

Asia WGS

AF:

0.166

AC:

579

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.7

(source)

DANN

Benign

0.47

PhyloP100

-0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over