1-111443384-C-A

Variant names:

• chr1-111443384-C-A
• rs116374713
• NM_024102.4:c.630G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4 BP6_Moderate BP7 BS2

The NM_024102.4(WDR77):​c.630G>T​(p.Ala210Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,552,362 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (48 hom.)
• Consequence: WDR77 NM_024102.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.953
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.213).
• BP6: Variant 1-111443384-C-A is Benign according to our data. Variant chr1-111443384-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.953 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 48 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR77	NM_024102.4	c.630G>T	p.Ala210Ala	synonymous_variant	Exon 7 of 10	ENST00000235090.10	NP_077007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR77	ENST00000235090.10	c.630G>T	p.Ala210Ala	synonymous_variant	Exon 7 of 10	1	NM_024102.4	ENSP00000235090.5
WDR77	ENST00000449340.1	c.438G>T	p.Ala146Ala	synonymous_variant	Exon 6 of 9	5		ENSP00000409300.1
WDR77	ENST00000459665.1	n.602G>T		non_coding_transcript_exon_variant	Exon 6 of 6	3
WDR77	ENST00000497278.5	n.285G>T		non_coding_transcript_exon_variant	Exon 5 of 9	3

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 565 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00644

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00346 AC: 545 AN: 157688 AF XY: 0.00360

Gnomad AFR exome AF: 0.000787

Gnomad AMR exome AF: 0.00141

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000455

Gnomad NFE exome AF: 0.00628

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00624 AC: 8737 AN: 1400056 Hom.: 48 Cov.: 31 AF XY: 0.00617 AC XY: 4258 AN XY: 690628

African (AFR) AF: 0.000663 AC: 21 AN: 31678

American (AMR) AF: 0.00137 AC: 49 AN: 35774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 35830

South Asian (SAS) AF: 0.00368 AC: 292 AN: 79262

European-Finnish (FIN) AF: 0.000872 AC: 43 AN: 49336

Middle Eastern (MID) AF: 0.000703 AC: 4 AN: 5688

European-Non Finnish (NFE) AF: 0.00746 AC: 8052 AN: 1079258

Other (OTH) AF: 0.00475 AC: 276 AN: 58046

GnomAD4 genome AF: 0.00372 AC: 566 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00340 AC XY: 253 AN XY: 74470

African (AFR) AF: 0.00164 AC: 68 AN: 41578

American (AMR) AF: 0.00209 AC: 32 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00644 AC: 438 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00408 Hom.: 1

Bravo AF: 0.00376

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WDR77: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116374713; hg19: chr1-111986006;