rs774822095

Variant names:

• chr7-122697892-C-G
• rs774822095
• NM_139175.2:c.1027G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-122697892-C-G
• chr7-122697892-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139175.2(RNF133):​c.1027G>C​(p.Ala343Pro) 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. 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. A343T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF133 NM_139175.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 0 publications found

Genes affected

RNF133 (HGNC:21154): (ring finger protein 133) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene has no intron. [provided by RefSeq, Jul 2008]

CADPS2 (HGNC:16018): (calcium dependent secretion activator 2) This gene encodes a member of the calcium-dependent activator of secretion (CAPS) protein family, which are calcium binding proteins that regulate the exocytosis of synaptic and dense-core vesicles in neurons and neuroendocrine cells. Mutations in this gene may contribute to autism susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065300554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139175.2. 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
	RNF133	NM_139175.2	MANE Select	c.1027G>C	p.Ala343Pro	missense	Exon 1 of 1	NP_631914.1	Q8WVZ7
	CADPS2	NM_017954.11	MANE Select	c.454-34323G>C		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.454-34323G>C		intron	N/A	NP_001350318.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF133	ENST00000340112.3	TSL:6 MANE Select	c.1027G>C	p.Ala343Pro	missense	Exon 1 of 1	ENSP00000344489.2	Q8WVZ7
	CADPS2	ENST00000449022.7	TSL:5 MANE Select	c.454-34323G>C		intron	N/A	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.454-34323G>C		intron	N/A	ENSP00000400401.2	Q86UW7-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.94
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.75
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0010
Sift	Uncertain	0.028	D
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.19		Gain of catalytic residue at P342 (P = 0.0126)
MVP		0.18
MPC		0.020
ClinPred		0.048	T
GERP RS		-0.67
Varity_R		0.11
gMVP		0.088
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774822095; hg19: chr7-122337946;