12-120557593-C-G

Variant names:

• chr12-120557593-C-G
• rs200683852
• NM_014868.5:c.878C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014868.5(RNF10):​c.878C>G​(p.Thr293Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF10	NM_014868.5	c.878C>G	p.Thr293Arg	missense_variant	Exon 6 of 17	ENST00000325954.9	NP_055683.3
RNF10	NM_001330474.2	c.878C>G	p.Thr293Arg	missense_variant	Exon 6 of 17		NP_001317403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF10	ENST00000325954.9	c.878C>G	p.Thr293Arg	missense_variant	Exon 6 of 17	1	NM_014868.5	ENSP00000322242.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251376 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135854

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS 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: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	35
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.84
MutPred		0.44		Gain of MoRF binding (P = 0.0167);Gain of MoRF binding (P = 0.0167);
MVP		0.79
MPC		0.81
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.90
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.79		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.79		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200683852; hg19: chr12-120995396;