Variant 1-145823794-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000582693.5(RNF115):c.80G>A(p.Gly27Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF115
ENST00000582693.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94

Variant links:

Genes affected

RNF115 (HGNC:18154): (ring finger protein 115) Enables ubiquitin-protein transferase activity. Involved in negative regulation of epidermal growth factor receptor signaling pathway; protein autoubiquitination; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RNF115 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF115	NM_014455.4 linkuse as main transcript	c.80G>A	p.Gly27Asp	missense_variant	1/9	ENST00000582693.5	NP_055270.1	Q9Y4L5
RNF115	XM_047418028.1 linkuse as main transcript	c.80G>A	p.Gly27Asp	missense_variant	1/6		XP_047273984.1
RNF115	XM_047418027.1 linkuse as main transcript	c.-105G>A		5_prime_UTR_variant	1/8		XP_047273983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF115	ENST00000582693.5 linkuse as main transcript	c.80G>A	p.Gly27Asp	missense_variant	1/9	1	NM_014455.4	ENSP00000463650.1		Q9Y4L5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1432110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712000

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.80G>A (p.G27D) alteration is located in exon 1 (coding exon 1) of the RNF115 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the glycine (G) at amino acid position 27 to be replaced by an aspartic acid (D). 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

Pathogenic

0.78

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.038

LIST_S2

Uncertain

0.88

MetaRNN

Uncertain

0.67

Sift4G

Benign

0.59

Vest4

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over