5-141980347-T-G

Variant names:

• chr5-141980347-T-G
• rs147059342
• NM_004290.5:c.1059T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004290.5(RNF14):​c.1059T>G​(p.Thr353Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,612,786 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00091 (7 hom.)
• Consequence: RNF14 NM_004290.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.711
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 5-141980347-T-G is Benign according to our data. Variant chr5-141980347-T-G is described in ClinVar as Benign. ClinVar VariationId is 791533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.711 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.1059T>G	p.Thr353Thr	synonymous	Exon 6 of 9	NP_004281.1	Q9UBS8-1
	RNF14	NM_001201365.2		c.1059T>G	p.Thr353Thr	synonymous	Exon 6 of 9	NP_001188294.1	Q9UBS8-1
	RNF14	NM_183399.3		c.1059T>G	p.Thr353Thr	synonymous	Exon 5 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.1059T>G	p.Thr353Thr	synonymous	Exon 6 of 9	ENSP00000378028.2	Q9UBS8-1
	RNF14	ENST00000356143.5	TSL:1	c.1059T>G	p.Thr353Thr	synonymous	Exon 5 of 8	ENSP00000348462.1	Q9UBS8-1
	RNF14	ENST00000394519.5	TSL:1	c.1059T>G	p.Thr353Thr	synonymous	Exon 6 of 9	ENSP00000378027.1	Q9UBS8-1

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 601 AN: 152244 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00159 AC: 399 AN: 250724 AF XY: 0.00134

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.000661

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.000909 AC: 1327 AN: 1460424 Hom.: 7 Cov.: 30 AF XY: 0.000877 AC XY: 637 AN XY: 726620

African (AFR) AF: 0.0137 AC: 458 AN: 33450

American (AMR) AF: 0.00210 AC: 94 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00287 AC: 75 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86226

European-Finnish (FIN) AF: 0.0000378 AC: 2 AN: 52978

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5766

European-Non Finnish (NFE) AF: 0.000460 AC: 511 AN: 1111096

Other (OTH) AF: 0.00215 AC: 130 AN: 60368

GnomAD4 genome AF: 0.00396 AC: 603 AN: 152362 Hom.: 4 Cov.: 33 AF XY: 0.00393 AC XY: 293 AN XY: 74512

African (AFR) AF: 0.0118 AC: 489 AN: 41588

American (AMR) AF: 0.00340 AC: 52 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00479

EpiCase AF: 0.000818

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.2
DANN	Benign	0.70
PhyloP100		-0.71
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147059342; hg19: chr5-141359912;