Variant 4-2497067-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002938.5(RNF4):c.70A>C(p.Thr24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

RNF4
NM_002938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0690

Variant links:

Genes affected

RNF4 (HGNC:10067): (ring finger protein 4) The protein encoded by this gene contains a RING finger motif and acts as a transcription regulator. This protein has been shown to interact with, and inhibit the activity of, TRPS1, a transcription suppressor of GATA-mediated transcription. Transcription repressor ZNF278/PATZ is found to interact with this protein, and thus reduce the enhancement of androgen receptor-dependent transcription mediated by this protein. Studies of the mouse and rat counterparts suggested a role of this protein in spermatogenesis. A pseudogene of this gene is found on chromosome 1.[provided by RefSeq, Jul 2010]

RNF4 links:

RNF4 (HGNC:):

RNF4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08112016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF4	NM_002938.5 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	3/8	ENST00000314289.13	NP_002929.1
RNF4	NM_001185009.3 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	4/9		NP_001171938.1
RNF4	NM_001185010.3 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	3/7		NP_001171939.1
RNF4	XM_047416062.1 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	4/9		XP_047272018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF4	ENST00000314289.13 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	3/8	1	NM_002938.5	ENSP00000315212.8		P78317-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151766

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74096

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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, 2023

The c.70A>C (p.T24P) alteration is located in exon 4 (coding exon 2) of the RNF4 gene. This alteration results from a A to C substitution at nucleotide position 70, causing the threonine (T) at amino acid position 24 to be replaced by a proline (P). 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

0.064

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.3

DANN

Benign

0.80

DEOGEN2

Benign

0.14

.;T;.;T;.;.;.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.48

T;.;T;T;T;T;.;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.081

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L;.;.;.;L;L;L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.25

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T;T;T;T;T;T

Polyphen

0.0, 0.0020

.;B;.;.;.;B;.;B;B;.

Vest4

0.12, 0.094, 0.12, 0.12

MutPred

0.21

Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);Gain of glycosylation at T20 (P = 0.0042);

MVP

0.56

MPC

0.63

ClinPred

0.033

GERP RS

-0.85

Varity_R

0.058

gMVP

0.14

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