Variant 12-120534868-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014868.5(RNF10):c.57C>A(p.Ser19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF10
NM_014868.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

RNF10 (HGNC:10055): (ring finger protein 10) The protein encoded by this gene contains a ring finger motif, which is known to be involved in protein-protein interactions. The specific function of this protein has not yet been determined. EST data suggests the existence of multiple alternatively spliced transcript variants, however, their full length nature is not known. [provided by RefSeq, Jul 2008]

RNF10 links:

LOC128071547 (HGNC:):

LOC128071547 links:

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ACMG classification

Classification made for transcript

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=0.31064773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF10	NM_014868.5 linkuse as main transcript	c.57C>A	p.Ser19Arg	missense_variant	1/17	ENST00000325954.9
LOC128071547	NM_001414895.1 linkuse as main transcript	c.172C>A	p.Arg58=	synonymous_variant	1/1	ENST00000675818.1
RNF10	NM_001330474.2 linkuse as main transcript	c.57C>A	p.Ser19Arg	missense_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF10	ENST00000325954.9 linkuse as main transcript	c.57C>A	p.Ser19Arg	missense_variant	1/17	1	NM_014868.5	P1	Q8N5U6-1
	ENST00000675818.1 linkuse as main transcript	c.172C>A	p.Arg58=	synonymous_variant	1/1		NM_001414895.1	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724538

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

Nov 23, 2022

The c.57C>A (p.S19R) alteration is located in exon 1 (coding exon 1) of the RNF10 gene. This alteration results from a C to A substitution at nucleotide position 57, causing the serine (S) at amino acid position 19 to be replaced by an arginine (R). 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

0.34

BayesDel_addAF

Benign

0.0084

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

T;T;T

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Uncertain

-0.074

MutationAssessor

Benign

1.4

L;.;L

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.071

T;D;T

Sift4G

Uncertain

0.031

D;D;D

Polyphen

0.0060

B;.;.

Vest4

0.18

MutPred

0.28

Loss of phosphorylation at S19 (P = 0.0024);Loss of phosphorylation at S19 (P = 0.0024);Loss of phosphorylation at S19 (P = 0.0024);

MVP

0.39

MPC

0.49

ClinPred

0.70

GERP RS

4.1

Varity_R

0.16

gMVP

0.27

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.

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