chr1-111441283-C-G

Variant names:

• chr1-111441283-C-G
• rs760102324
• NM_024102.4:c.976G>C

Variant summary

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

The NM_024102.4(WDR77):​c.976G>C​(p.Val326Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V326I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WDR77 NM_024102.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• Publications: 0 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]

ENSG00000243960 (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=0.07355344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR77	NM_024102.4	c.976G>C	p.Val326Leu	missense_variant	Exon 10 of 10	ENST00000235090.10	NP_077007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR77	ENST00000235090.10	c.976G>C	p.Val326Leu	missense_variant	Exon 10 of 10	1	NM_024102.4	ENSP00000235090.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1434992 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 713766

African (AFR) AF: 0.00 AC: 0 AN: 32288

American (AMR) AF: 0.00 AC: 0 AN: 41456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25526

East Asian (EAS) AF: 0.00 AC: 0 AN: 37966

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1097314

Other (OTH) AF: 0.00 AC: 0 AN: 59072

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.3
DANN	Benign	0.89
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.21
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.076
Sift	Benign	0.38	T
Sift4G	Benign	0.59	T
Polyphen		0.0010	B
Vest4		0.052
MutPred		0.44		Gain of sheet (P = 0.0827);
MVP		0.56
MPC		0.26
ClinPred		0.042	T
GERP RS		-4.2
Varity_R		0.043
gMVP		0.094
Mutation Taster		=85/15	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: rs760102324; hg19: chr1-111983905;