6-13977348-G-A

Position:

• chr6-13977348-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152737.4(RNF182):​c.229G>A​(p.Glu77Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF182 NM_152737.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3091141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF182	NM_152737.4	c.229G>A	p.Glu77Lys	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.229G>A	p.Glu77Lys	missense_variant	3/3	1	NM_152737.4	ENSP00000420465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 06, 2022

The c.229G>A (p.E77K) alteration is located in exon 4 (coding exon 1) of the RNF182 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the glutamic acid (E) at amino acid position 77 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T;.;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	.;.;.;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	2.0	M;M;M;.;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.028	D;D;D;D;D;D
Sift4G	Uncertain	0.060	T;T;T;T;T;T
Polyphen		0.90	P;P;P;.;.;P
Vest4		0.11
MutPred		0.38		Gain of ubiquitination at E77 (P = 0.017);Gain of ubiquitination at E77 (P = 0.017);Gain of ubiquitination at E77 (P = 0.017);Gain of ubiquitination at E77 (P = 0.017);Gain of ubiquitination at E77 (P = 0.017);Gain of ubiquitination at E77 (P = 0.017);
MVP		0.91
MPC		0.36
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.17
gMVP		0.49

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: chr6-13977579;