Genetic Variant RNF10:p.Ser19Arg (chr12-120534868-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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

Publications

0 publications found

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:0):

LOC128071547 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein
RNF10	NM_014868.5 link	c.57C>A	p.Ser19Arg	missense_variant	Exon 1 of 17	ENST00000325954.9	NP_055683.3
LOC128071547	NM_001414895.1 link	c.172C>A	p.Arg58Arg	synonymous_variant	Exon 1 of 1	ENST00000675818.1	NP_001401824.1
RNF10	NM_001330474.2 link	c.57C>A	p.Ser19Arg	missense_variant	Exon 1 of 17		NP_001317403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF10	ENST00000325954.9 link	c.57C>A	p.Ser19Arg	missense_variant	Exon 1 of 17	1	NM_014868.5	ENSP00000322242.4
ENSG00000288623	ENST00000675818.1 link	c.172C>A	p.Arg58Arg	synonymous_variant	Exon 1 of 1		NM_001414895.1	ENSP00000502390.1

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

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111558

Other (OTH)

AF:

0.00

AC:

AN:

60228

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

Nov 23, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

2.5

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

PromoterAI

-0.0041

Neutral

(source)

Varity_R

0.16

gMVP

0.27

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over