Variant 12-120534953-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014868.5(RNF10):c.142T>G(p.Ser48Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000288 in 1,599,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

RNF10
NM_014868.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04667154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RNF10	NM_014868.5 linkuse as main transcript	c.142T>G	p.Ser48Ala	missense_variant	1/17	ENST00000325954.9
LOC128071547	NM_001414895.1 linkuse as main transcript	c.257T>G	p.Val86Gly	missense_variant	1/1	ENST00000675818.1
RNF10	NM_001330474.2 linkuse as main transcript	c.142T>G	p.Ser48Ala	missense_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF10	ENST00000325954.9 linkuse as main transcript	c.142T>G	p.Ser48Ala	missense_variant	1/17	1	NM_014868.5	P1	Q8N5U6-1
	ENST00000675818.1 linkuse as main transcript	c.257T>G	p.Val86Gly	missense_variant	1/1		NM_001414895.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000718

AC:

AN:

222958

Hom.:

AF XY:

0.0000806

AC XY:

AN XY:

124022

show subpopulations

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:

0.000536

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1447450

Hom.:

Cov.:

AF XY:

0.0000430

AC XY:

AN XY:

720460

show subpopulations

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:

0.000443

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000837

AC:

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 10, 2022

The c.142T>G (p.S48A) alteration is located in exon 1 (coding exon 1) of the RNF10 gene. This alteration results from a T to G substitution at nucleotide position 142, causing the serine (S) at amino acid position 48 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

T;T;T

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Uncertain

-0.049

MutationAssessor

Benign

1.8

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.75

N;N;N

REVEL

Uncertain

0.43

Sift

Benign

0.37

T;D;T

Sift4G

Benign

0.34

T;D;T

Polyphen

0.94

P;.;.

Vest4

0.23

MutPred

0.21

Loss of phosphorylation at S48 (P = 0.0019);Loss of phosphorylation at S48 (P = 0.0019);Loss of phosphorylation at S48 (P = 0.0019);

MVP

0.79

MPC

0.19

ClinPred

0.49

GERP RS

5.1

Varity_R

0.23

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over