5-141959262-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000511961.5(RNF14):c.-7+837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 151,976 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.091 (757 hom., cov: 33)
• Consequence: RNF14 ENST00000511961.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

Genes affected

RNF14 (HGNC:10058): (ring finger protein 14) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein interacts with androgen receptor (AR) and may function as a coactivator that induces AR target gene expression in prostate. A dominant negative mutant of this gene has been demonstrated to inhibit the AR-mediated growth of prostate cancer. This protein also interacts with class III ubiquitin-conjugating enzymes (E2s) and may act as a ubiquitin-ligase (E3) in the ubiquitination of certain nuclear proteins. Six alternatively spliced transcript variants encoding two distinct isoforms have been reported. [provided by RefSeq, Jan 2011]

PCDH12 (HGNC:8657): (protocadherin 12) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 5-141959262-G-A is Benign according to our data. Variant chr5-141959262-G-A is described in ClinVar as [Benign]. Clinvar id is 1287449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF14	XM_047417903.1	c.-181+837G>A		intron_variant
RNF14	XM_047417904.1	c.-181+9852G>A		intron_variant
RNF14	XM_047417908.1	c.-181+9852G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF14	ENST00000506822.5	c.-181+837G>A		intron_variant		5
RNF14	ENST00000511961.5	c.-7+837G>A		intron_variant		3
PCDH12	ENST00000512221.2	n.259-1017C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13861 AN: 151858 Hom.: 757 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0912 AC: 13866 AN: 151976 Hom.: 757 Cov.: 33 AF XY: 0.0923 AC XY: 6857 AN XY: 74268

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.0761

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.0942

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.106 Hom.: 306

Bravo AF: 0.0864

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.094
Dann	Benign	0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3761762; hg19: chr5-141338827; COSMIC: COSV51520287;