chr7-122697889-C-T

Variant names:

• chr7-122697889-C-T
• rs914476772
• NM_139175.2:c.1030G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_139175.2(RNF133):​c.1030G>A​(p.Gly344Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,498 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RNF133 NM_139175.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.596
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052209675).
• BP6: Variant 7-122697889-C-T is Benign according to our data. Variant chr7-122697889-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3155027.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1030G>A	p.Gly344Arg	missense	Exon 1 of 1	NP_631914.1	Q8WVZ7
	CADPS2	NM_017954.11	MANE Select	c.454-34320G>A		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.454-34320G>A		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.1030G>A	p.Gly344Arg	missense	Exon 1 of 1	ENSP00000344489.2	Q8WVZ7
	CADPS2	ENST00000449022.7	TSL:5 MANE Select	c.454-34320G>A		intron	N/A	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.454-34320G>A		intron	N/A	ENSP00000400401.2	Q86UW7-2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.000480

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251156 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461394 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727006

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111614

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.000458 AC: 7 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.0000427 Hom.: 0

Bravo AF: 0.000136

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.065
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.55
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-0.60
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.020
Sift	Benign	0.27	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.31		Gain of sheet (P = 0.0149)
MVP		0.15
MPC		0.020
ClinPred		0.027	T
GERP RS		-1.2
Varity_R		0.052
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs914476772; hg19: chr7-122337943;