chr12-120534842-A-C

Variant names:

• chr12-120534842-A-C
• rs747471809
• NM_014868.5:c.31A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330474.2(RNF10):​c.31A>C​(p.Thr11Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T11A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF10 NM_001330474.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 1 publications found

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]

LOC128071547 (HGNC:0):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20438516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330474.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	NM_014868.5	MANE Select	c.31A>C	p.Thr11Pro	missense	Exon 1 of 17	NP_055683.3
	LOC128071547	NM_001414895.1	MANE Select	c.146A>C	p.His49Pro	missense	Exon 1 of 1	NP_001401824.1
	RNF10	NM_001330474.2		c.31A>C	p.Thr11Pro	missense	Exon 1 of 17	NP_001317403.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	ENST00000325954.9	TSL:1 MANE Select	c.31A>C	p.Thr11Pro	missense	Exon 1 of 17	ENSP00000322242.4
	ENSG00000288623	ENST00000675818.1	MANE Select	c.146A>C	p.His49Pro	missense	Exon 1 of 1	ENSP00000502390.1
	RNF10	ENST00000413266.6	TSL:5	c.31A>C	p.Thr11Pro	missense	Exon 1 of 17	ENSP00000415682.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.35	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.021	D
Polyphen		0.44	B
Vest4		0.095
MutPred		0.078		Loss of phosphorylation at T11 (P = 0.0335)
MVP		0.66
MPC		0.33
ClinPred		0.10	T
GERP RS		2.4
PromoterAI		-0.11	Neutral
Varity_R		0.096
gMVP		0.25
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs747471809; hg19: chr12-120972645;