6-13977477-A-G

Position:

• chr6-13977477-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152737.4(RNF182):​c.358A>G​(p.Ser120Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF182 NM_152737.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

Genes affected

RNF182 (HGNC:28522): (ring finger protein 182) Enables ubiquitin-protein transferase activity. Involved in protein ubiquitination. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19049042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF182	NM_152737.4	c.358A>G	p.Ser120Gly	missense_variant	3/3	ENST00000488300.6	NP_689950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF182	ENST00000488300.6	c.358A>G	p.Ser120Gly	missense_variant	3/3	1	NM_152737.4	ENSP00000420465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.358A>G (p.S120G) alteration is located in exon 4 (coding exon 1) of the RNF182 gene. This alteration results from a A to G substitution at nucleotide position 358, causing the serine (S) at amino acid position 120 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.74	.;.;.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.8	L;L;L;.;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.82	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.040	D;D;D;D;D
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.0	B;B;B;.;B
Vest4		0.067
MutPred		0.31		Gain of catalytic residue at S120 (P = 0.0024);Gain of catalytic residue at S120 (P = 0.0024);Gain of catalytic residue at S120 (P = 0.0024);Gain of catalytic residue at S120 (P = 0.0024);Gain of catalytic residue at S120 (P = 0.0024);
MVP		0.90
MPC		0.16
ClinPred		0.64	D
GERP RS		5.3
Varity_R		0.14
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-13977708;