chr12-56104457-G-T

Variant names:

• chr12-56104457-G-T
• rs773121
• ENST00000548861.2:c.32-2131G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000548861.2(ENSG00000257411):​c.32-2131G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ENSG00000257411 ENST00000548861.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

ENSG00000257411 (HGNC:):

PA2G4 (HGNC:8550): (proliferation-associated 2G4) This gene encodes an RNA-binding protein that is involved in growth regulation. This protein is present in pre-ribosomal ribonucleoprotein complexes and may be involved in ribosome assembly and the regulation of intermediate and late steps of rRNA processing. This protein can interact with the cytoplasmic domain of the ErbB3 receptor and may contribute to transducing growth regulatory signals. This protein is also a transcriptional co-repressor of androgen receptor-regulated genes and other cell cycle regulatory genes through its interactions with histone deacetylases. This protein has been implicated in growth inhibition and the induction of differentiation of human cancer cells. Six pseudogenes, located on chromosomes 3, 6, 9, 18, 20 and X, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PA2G4	NM_006191.3	c.-281G>T		upstream_gene_variant		ENST00000303305.11	NP_006182.2
LOC105369782	XR_944995.4	n.-38C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257411	ENST00000548861.2	c.32-2131G>T		intron_variant	Intron 1 of 5	5		ENSP00000449770.3
PA2G4	ENST00000303305.11	c.-281G>T		upstream_gene_variant		1	NM_006191.3	ENSP00000302886.6
PA2G4	ENST00000552766.5	c.-281G>T		upstream_gene_variant		5		ENSP00000448557.1
ENSG00000257553	ENST00000548595.1	n.*157C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs773121; hg19: chr12-56498241;