12-120534953-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S48P) has been classified 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

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RNF10	NM_014868.5 link	c.142T>G	p.Ser48Ala	missense_variant	Exon 1 of 17	ENST00000325954.9	NP_055683.3
LOC128071547	NM_001414895.1 link	c.257T>G	p.Val86Gly	missense_variant	Exon 1 of 1	ENST00000675818.1	NP_001401824.1
RNF10	NM_001330474.2 link	c.142T>G	p.Ser48Ala	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.142T>G	p.Ser48Ala	missense_variant	Exon 1 of 17	1	NM_014868.5	ENSP00000322242.4
ENSG00000288623	ENST00000675818.1 link	c.257T>G	p.Val86Gly	missense_variant	Exon 1 of 1		NM_001414895.1	ENSP00000502390.1

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

GnomAD2 exomes

AF:

0.0000718

AC:

AN:

222958

AF XY:

0.0000806

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 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

African (AFR)

AF:

0.00

AC:

AN:

33266

American (AMR)

AF:

0.00

AC:

AN:

44364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.000443

AC:

AN:

85810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110690

Other (OTH)

AF:

0.0000166

AC:

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41510

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

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

Sep 11, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

5.1

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

PromoterAI

0.039

Neutral

(source)

Varity_R

0.23

gMVP

0.22

Mutation Taster

=84/16

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over