5-141974950-A-G

Variant names:

• chr5-141974950-A-G
• rs150500657
• NM_004290.5:c.301A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004290.5(RNF14):​c.301A>G​(p.Thr101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T101S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: RNF14 NM_004290.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 0 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]

ENSG00000254099 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0786908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004290.5. 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
	RNF14	NM_004290.5	MANE Select	c.301A>G	p.Thr101Ala	missense	Exon 4 of 9	NP_004281.1	Q9UBS8-1
	RNF14	NM_001201365.2		c.301A>G	p.Thr101Ala	missense	Exon 4 of 9	NP_001188294.1	Q9UBS8-1
	RNF14	NM_183399.3		c.301A>G	p.Thr101Ala	missense	Exon 3 of 8	NP_899646.1	Q9UBS8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF14	ENST00000394520.7	TSL:1 MANE Select	c.301A>G	p.Thr101Ala	missense	Exon 4 of 9	ENSP00000378028.2	Q9UBS8-1
	RNF14	ENST00000356143.5	TSL:1	c.301A>G	p.Thr101Ala	missense	Exon 3 of 8	ENSP00000348462.1	Q9UBS8-1
	RNF14	ENST00000394519.5	TSL:1	c.301A>G	p.Thr101Ala	missense	Exon 4 of 9	ENSP00000378027.1	Q9UBS8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250590 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000876

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461116 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 726892

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.0000225 AC: 1 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111826

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.57	N
PhyloP100		2.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.064
Sift	Benign	0.98	T
Sift4G	Benign	0.90	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.44		Loss of sheet (P = 0.0457)
MVP		0.29
MPC		0.38
ClinPred		0.17	T
GERP RS		4.4
Varity_R		0.029
gMVP		0.17
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150500657; hg19: chr5-141354515;