chr5-141983457-A-G

Position:

• chr5-141983457-A-G

Variant summary

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

The ENST00000394520.7(RNF14):​c.1141A>G​(p.Lys381Glu) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: RNF14 ENST00000394520.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.06

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]

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	Protein	UniProt
RNF14	NM_004290.5	c.1141A>G	p.Lys381Glu	missense_variant	7/9	ENST00000394520.7	NP_004281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF14	ENST00000394520.7	c.1141A>G	p.Lys381Glu	missense_variant	7/9	1	NM_004290.5	ENSP00000378028.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 14, 2024

The c.1141A>G (p.K381E) alteration is located in exon 7 (coding exon 5) of the RNF14 gene. This alteration results from a A to G substitution at nucleotide position 1141, causing the lysine (K) at amino acid position 381 to be replaced by a glutamic acid (E). 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	0.22
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T;T;.;T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	.;.;D;.;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.2	M;M;M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	D;D;D;D;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;T
Polyphen		0.54	P;P;P;P;.;.
Vest4		0.80
MutPred		0.45		Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);.;.;
MVP		0.91
MPC		1.1
ClinPred		0.94	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.57
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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: chr5-141363022;