chr6-13977582-C-T

Variant names:

• chr6-13977582-C-T
• rs1245396002
• NM_152737.4:c.463C>T

Variant summary

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

The NM_152737.4(RNF182):​c.463C>T​(p.Pro155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P155T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF182 NM_152737.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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=0.17780489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF182	NM_152737.4	c.463C>T	p.Pro155Ser	missense_variant	Exon 3 of 3	ENST00000488300.6	NP_689950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF182	ENST00000488300.6	c.463C>T	p.Pro155Ser	missense_variant	Exon 3 of 3	1	NM_152737.4	ENSP00000420465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251260 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135798

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.059	T;T;T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0059
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	.;.;.;D;D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.69	N;N;N;.;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.33	T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T
Polyphen		0.21	B;B;B;.;B
Vest4		0.065
MutPred		0.25		Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);
MVP		0.89
MPC		0.13
ClinPred		0.26	T
GERP RS		5.0
Varity_R		0.12
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs1245396002; hg19: chr6-13977813;