rs1427222454

Variant names:

• chr1-111449084-C-G
• rs1427222454
• NM_024102.4:c.86G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-111449084-C-G
• chr1-111449084-C-T

Variant summary

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

The NM_024102.4(WDR77):​c.86G>C​(p.Arg29Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,824 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R29Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR77 NM_024102.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• 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]

ATP5PB (HGNC:840): (ATP synthase peripheral stalk-membrane subunit b) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR77	NM_024102.4	c.86G>C	p.Arg29Pro	missense_variant	Exon 1 of 10	ENST00000235090.10	NP_077007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR77	ENST00000235090.10	c.86G>C	p.Arg29Pro	missense_variant	Exon 1 of 10	1	NM_024102.4	ENSP00000235090.5
ATP5PB	ENST00000493119.5	n.87-111C>G		intron_variant	Intron 1 of 4	3
WDR77	ENST00000459665.1	n.-193G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451824 Hom.: 0 Cov.: 49 AF XY: 0.00000139 AC XY: 1 AN XY: 721558

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39424

South Asian (SAS) AF: 0.00 AC: 0 AN: 84672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49922

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108854

Other (OTH) AF: 0.0000167 AC: 1 AN: 59974

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.36		Loss of sheet (P = 7e-04);
MVP		0.82
MPC		0.99
ClinPred		0.98	D
GERP RS		4.3
PromoterAI		0.029	Neutral
Varity_R		0.89
gMVP		0.83
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1427222454; hg19: chr1-111991706;