Genetic Variant RNF10:p.Ile138Asn (chr12-120552557-TC-AT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_014868.5(RNF10):c.413_414delTCinsAT (p.Ile138Asn) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 7.63). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.I138N: Uncertain_significance (ClinVar VariationId 2597659, 1 star)

Frequency

Genomes: not found (cov: 31)

Consequence

RNF10
NM_014868.5 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.63

Publications

0 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:

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new If you want to explore the variant's impact on the transcript NM_014868.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_014868.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RNF10 NM_014868.5	MANE Select	c.413_414delTCinsAT p.Ile138Asn	missense	N/A	Prot: NP_055683.3
	RNF10 NM_001330474.2		c.413_414delTCinsAT p.Ile138Asn	missense	N/A	Prot: NP_001317403.1 UniProt: Q8N5U6-2

RNF10 NM_014868.5

MANE Select

HGVSc / HGVSpc.413_414delTCinsATp.Ile138Asn

Exon rankN/A

missense

Prot: NP_055683.3

RNF10 NM_001330474.2

HGVSc / HGVSpc.413_414delTCinsATp.Ile138Asn

Exon rankN/A

missense

Prot: NP_001317403.1UniProt: Q8N5U6-2

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
RNF10 ENST00000325954.9	TSL:1MANE Select	c.413_414delTCinsAT p.Ile138Asn	missense	N/A	Prot: ENSP00000322242.4 UniProt: Q8N5U6-1
RNF10 ENST00000413266.6	TSL:5	c.413_414delTCinsAT p.Ile138Asn	missense	N/A	Prot: ENSP00000415682.2 UniProt: Q8N5U6-2
RNF10 ENST00000537997.1	TSL:4	c.263_264delTCinsAT p.Ile88Asn	missense	N/A	Prot: ENSP00000443235.1 UniProt: F5H5P6

RNF10 ENST00000325954.9

TSL:1MANE Select

HGVSc / HGVSpc.413_414delTCinsATp.Ile138Asn

Exon rankN/A

missense

Prot: ENSP00000322242.4UniProt: Q8N5U6-1

RNF10 ENST00000413266.6

TSL:5

HGVSc / HGVSpc.413_414delTCinsATp.Ile138Asn

Exon rankN/A

missense

Prot: ENSP00000415682.2UniProt: Q8N5U6-2

RNF10 ENST00000537997.1

TSL:4

HGVSc / HGVSpc.263_264delTCinsATp.Ile88Asn

Exon rankN/A

missense

Prot: ENSP00000443235.1UniProt: F5H5P6

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	7.6

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence