Variant 5-141978730-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000394520.7(RNF14):c.734C>A(p.Ala245Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RNF14
ENST00000394520.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

Variant links:

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]

RNF14 links:

RNF14 (HGNC:):

RNF14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF14	NM_004290.5 linkuse as main transcript	c.734C>A	p.Ala245Asp	missense_variant	5/9	ENST00000394520.7	NP_004281.1	Q9UBS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF14	ENST00000394520.7 linkuse as main transcript	c.734C>A	p.Ala245Asp	missense_variant	5/9	1	NM_004290.5	ENSP00000378028.2		Q9UBS8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251158

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.734C>A (p.A245D) alteration is located in exon 5 (coding exon 3) of the RNF14 gene. This alteration results from a C to A substitution at nucleotide position 734, causing the alanine (A) at amino acid position 245 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

T;T;T;T;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.70

T;.;.;T;.;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.45

T;T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.6

.;L;L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.50

N;N;N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.40

T;T;T;T;T;T

Sift4G

Uncertain

0.030

D;T;T;T;T;T

Polyphen

0.026

.;B;B;B;B;.

Vest4

0.37, 0.37, 0.37

MutPred

0.59

Loss of catalytic residue at A245 (P = 0.0065);Loss of catalytic residue at A245 (P = 0.0065);Loss of catalytic residue at A245 (P = 0.0065);Loss of catalytic residue at A245 (P = 0.0065);Loss of catalytic residue at A245 (P = 0.0065);.;

MVP

0.91

MPC

0.58

ClinPred

0.31

GERP RS

5.4

Varity_R

0.25

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over