12-120566865-T-G

Variant names:

• chr12-120566865-T-G
• NM_014868.5:c.1926T>G
• RNF10 p.Phe642Leu

Variant summary

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

The NM_014868.5(RNF10):​c.1926T>G​(p.Phe642Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014868.5. 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.1926T>G	p.Phe642Leu	missense	Exon 13 of 17	NP_055683.3
	RNF10	NM_001330474.2		c.1941T>G	p.Phe647Leu	missense	Exon 13 of 17	NP_001317403.1	Q8N5U6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	ENST00000325954.9	TSL:1 MANE Select	c.1926T>G	p.Phe642Leu	missense	Exon 13 of 17	ENSP00000322242.4	Q8N5U6-1
	RNF10	ENST00000413266.6	TSL:5	c.1941T>G	p.Phe647Leu	missense	Exon 13 of 17	ENSP00000415682.2	Q8N5U6-2
	RNF10	ENST00000540046.5	TSL:3	c.558T>G	p.Phe186Leu	missense	Exon 5 of 5	ENSP00000439859.1	H0YFQ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.072	T
Varity_R		0.37
gMVP		0.60
Mutation Taster		=15/85	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-121004668;