3-141738375-G-T

Variant names:

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

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>T​(p.Ala12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,591,934 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (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=0.09114638).

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>T	p.Ala12Ser	missense	Exon 1 of 3	NP_055060.1	Q9UBF6-1
	RNF7	NM_001201370.2		c.34G>T	p.Ala12Ser	missense	Exon 1 of 2	NP_001188299.1	Q9UBF6-4
	RNF7	NM_183237.3		c.34G>T	p.Ala12Ser	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>T	p.Ala12Ser	missense	Exon 1 of 3	ENSP00000273480.3	Q9UBF6-1
	RNF7	ENST00000477012.5	TSL:1	n.34G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000419339.1	Q9UBF6-2
	RNF7	ENST00000480908.1	TSL:4	c.34G>T	p.Ala12Ser	missense	Exon 1 of 2	ENSP00000419084.1	Q9UBF6-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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 AF: 6.95e-7 AC: 1 AN: 1439704 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 714356

African (AFR) AF: 0.0000305 AC: 1 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: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1101746

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.0000241 AC: 1 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.052
Sift	Benign	0.44	T
Sift4G	Benign	0.81	T
Polyphen		0.039	B
Vest4		0.11
MVP		0.47
MPC		0.90
ClinPred		0.20	T
GERP RS		1.8
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.21
Mutation Taster		=96/4	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;