Variant 4-2512512-G-A 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.289G>A(p.Asp97Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RNF4
NM_002938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

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:

ENSG00000290180 (HGNC:):

ENSG00000290180 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=0.25568378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF4	NM_002938.5 linkuse as main transcript	c.289G>A	p.Asp97Asn	missense_variant	6/8	ENST00000314289.13	NP_002929.1
RNF4	NM_001185009.3 linkuse as main transcript	c.289G>A	p.Asp97Asn	missense_variant	7/9		NP_001171938.1
RNF4	XM_047416062.1 linkuse as main transcript	c.289G>A	p.Asp97Asn	missense_variant	7/9		XP_047272018.1
RNF4	NM_001185010.3 linkuse as main transcript	c.214+547G>A		intron_variant			NP_001171939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF4	ENST00000314289.13 linkuse as main transcript	c.289G>A	p.Asp97Asn	missense_variant	6/8	1	NM_002938.5	ENSP00000315212.8		P78317-1
ENSG00000290180	ENST00000703446.1 linkuse as main transcript	n.34G>A		non_coding_transcript_exon_variant	1/5			ENSP00000515299.1		H0YAI5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249038

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS 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:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

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 15, 2024

The c.289G>A (p.D97N) alteration is located in exon 7 (coding exon 5) of the RNF4 gene. This alteration results from a G to A substitution at nucleotide position 289, causing the aspartic acid (D) at amino acid position 97 to be replaced by an asparagine (N). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

.;D;.;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

M;.;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.018

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.78

P;.;P;P

Vest4

0.19

MutPred

0.22

Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);

MVP

0.63

MPC

1.1

ClinPred

0.78

GERP RS

4.7

Varity_R

0.15

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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