chr4-2512588-C-T

Variant names:

• chr4-2512588-C-T
• rs1560415420
• NM_002938.5:c.365C>T

Variant summary

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

The NM_002938.5(RNF4):​c.365C>T​(p.Thr122Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF4 NM_002938.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

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]

ENSG00000290180 (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=0.108380646).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002938.5. 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
	RNF4	NM_002938.5	MANE Select	c.365C>T	p.Thr122Ile	missense	Exon 6 of 8	NP_002929.1	P78317-1
	RNF4	NM_001185009.3		c.365C>T	p.Thr122Ile	missense	Exon 7 of 9	NP_001171938.1	P78317-1
	RNF4	NM_001185010.3		c.215-495C>T		intron	N/A	NP_001171939.1	P78317-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF4	ENST00000314289.13	TSL:1 MANE Select	c.365C>T	p.Thr122Ile	missense	Exon 6 of 8	ENSP00000315212.8	P78317-1
	RNF4	ENST00000506706.5	TSL:1	c.365C>T	p.Thr122Ile	missense	Exon 7 of 9	ENSP00000424076.1	P78317-1
	RNF4	ENST00000511859.5	TSL:1	c.215-495C>T		intron	N/A	ENSP00000426615.1	P78317-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	0.032	D
Sift4G	Benign	0.19	T
Polyphen		0.015	B
Vest4		0.081
MutPred		0.30		Loss of disorder (P = 0.0502)
MVP		0.33
MPC		0.59
ClinPred		0.14	T
GERP RS		4.5
Varity_R		0.12
gMVP		0.29
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1560415420; hg19: chr4-2514315;