5-141965653-T-C

Variant names:

• chr5-141965653-T-C
• rs252139
• ENST00000511961.5:c.-7+7228T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000511961.5(RNF14):​c.-7+7228T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,286 control chromosomes in the GnomAD database, including 59,784 homozygotes. 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: 𝑓 0.88 (59784 hom., cov: 33)
• Consequence: RNF14 ENST00000511961.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 8 publications found

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]

PCDH12 Gene-Disease associations (from GenCC):

• diencephalic-mesencephalic junction dysplasia syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• diencephalic-mesencephalic junction dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124901095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511961.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF14	ENST00000511961.5	TSL:3	c.-7+7228T>C		intron	N/A	ENSP00000423420.1	D6RA38
	RNF14	ENST00000506822.5	TSL:5	c.-180-5051T>C		intron	N/A	ENSP00000423273.1	D6R996
	PCDH12	ENST00000512221.2	TSL:3	n.135-2439A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134503 AN: 152168 Hom.: 59721 Cov.: 33

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.884 AC: 134624 AN: 152286 Hom.: 59784 Cov.: 33 AF XY: 0.884 AC XY: 65846 AN XY: 74454

African (AFR) AF: 0.959 AC: 39873 AN: 41574

American (AMR) AF: 0.912 AC: 13953 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2886 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5072 AN: 5176

South Asian (SAS) AF: 0.903 AC: 4362 AN: 4828

European-Finnish (FIN) AF: 0.801 AC: 8495 AN: 10600

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57213 AN: 68020

Other (OTH) AF: 0.878 AC: 1851 AN: 2108

Alfa AF: 0.847 Hom.: 24184

Bravo AF: 0.896

Asia WGS AF: 0.925 AC: 3216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.84
PhyloP100		0.51

Splicing

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

Other links and lift over

dbSNP: rs252139; hg19: chr5-141345218;