3-141738375-G-C

Variant names:

• chr3-141738375-G-C
• rs759352977
• NM_014245.5:c.34G>C

Variant summary

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

The NM_014245.5(RNF7):​c.34G>C​(p.Ala12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,704 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. A12T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF7 NM_014245.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

Genes affected

RNF7 (HGNC:10070): (ring finger protein 7) The protein encoded by this gene is a highly conserved ring finger protein. It is an essential subunit of SKP1-cullin/CDC53-F box protein ubiquitin ligases, which are a part of the protein degradation machinery important for cell cycle progression and signal transduction. This protein interacts with, and is a substrate of, casein kinase II (CSNK2A1/CKII). The phosphorylation of this protein by CSNK2A1 has been shown to promote the degradation of IkappaBalpha (CHUK/IKK-alpha/IKBKA) and p27Kip1(CDKN1B). Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ENSG00000285558 (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=0.12367952).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014245.5. 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
	RNF7	NM_014245.5	MANE Select	c.34G>C	p.Ala12Pro	missense	Exon 1 of 3	NP_055060.1	Q9UBF6-1
	RNF7	NM_001201370.2		c.34G>C	p.Ala12Pro	missense	Exon 1 of 2	NP_001188299.1	Q9UBF6-4
	RNF7	NM_183237.3		c.34G>C	p.Ala12Pro	missense	Exon 1 of 3	NP_899060.1	Q9UBF6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF7	ENST00000273480.4	TSL:1 MANE Select	c.34G>C	p.Ala12Pro	missense	Exon 1 of 3	ENSP00000273480.3	Q9UBF6-1
	RNF7	ENST00000477012.5	TSL:1	n.34G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000419339.1	Q9UBF6-2
	RNF7	ENST00000480908.1	TSL:4	c.34G>C	p.Ala12Pro	missense	Exon 1 of 2	ENSP00000419084.1	Q9UBF6-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439704 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 714356

African (AFR) AF: 0.00 AC: 0 AN: 32790

American (AMR) AF: 0.00 AC: 0 AN: 41398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25652

East Asian (EAS) AF: 0.00 AC: 0 AN: 38196

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101746

Other (OTH) AF: 0.00 AC: 0 AN: 59484

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.14
Sift	Benign	0.27	T
Sift4G	Benign	0.29	T
Polyphen		0.38	B
Vest4		0.074
MutPred		0.15		Loss of catalytic residue at S17 (P = 0.0996)
MVP		0.62
MPC		1.4
ClinPred		0.30	T
GERP RS		1.8
PromoterAI		-0.11	Neutral
Varity_R		0.11
gMVP		0.48
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs759352977; hg19: chr3-141457217;