5-141980349-C-T

Variant summary

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

The NM_004290.5(RNF14):c.1061C>T(p.Ala354Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF14 NM_004290.5 missense, splice_region
• Scores: Splicing: ADA: 0.9906
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

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]

(HGNC:):

ACMG classification

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	UniProt
RNF14	NM_004290.5	c.1061C>T	p.Ala354Val	missense_variant, splice_region_variant	6/9	ENST00000394520.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF14	ENST00000394520.7	c.1061C>T	p.Ala354Val	missense_variant, splice_region_variant	6/9	1	NM_004290.5	P1
	ENST00000520882.1	n.156+1253G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.1061C>T (p.A354V) alteration is located in exon 6 (coding exon 4) of the RNF14 gene. This alteration results from a C to T substitution at nucleotide position 1061, causing the alanine (A) at amino acid position 354 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.2	M;M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.081	T;T;T;T;T
Sift4G	Benign	0.22	T;T;T;T;T
Polyphen		0.67	P;P;P;P;.
Vest4		0.46
MutPred		0.45		Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);.;
MVP		0.79
MPC		0.53
ClinPred		0.91	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.27
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.85
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-141359914;