12-120534893-T-A

Variant names:

• chr12-120534893-T-A
• NM_014868.5:c.82T>A
• RNF10 p.Ser28Thr

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACMG Germline Pathogenicity v2019). PM2BP4

The NM_014868.5(RNF10):c.82T>A (p.Ser28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61
• 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]

LOC128071547 (HGNC:0):

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Uncertain_significance. The variant received 1 points.

• PM2: Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
• BP4: Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Supporting).

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.82T>A	p.Ser28Thr	missense	Exon 1 of 17	NP_055683.3
	LOC128071547	NM_001414895.1	MANE Select	c.197T>A	p.Phe66Tyr	missense	Exon 1 of 1	NP_001401824.1	A0A6Q8PGS0
	RNF10	NM_001330474.2		c.82T>A	p.Ser28Thr	missense	Exon 1 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.82T>A	p.Ser28Thr	missense	Exon 1 of 17	ENSP00000322242.4	Q8N5U6-1
	ENSG00000288623	ENST00000675818.1	MANE Select	c.197T>A	p.Phe66Tyr	missense	Exon 1 of 1	ENSP00000502390.1	A0A6Q8PGS0
	RNF10	ENST00000413266.6	TSL:5	c.82T>A	p.Ser28Thr	missense	Exon 1 of 17	ENSP00000415682.2	Q8N5U6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.25
Sift	Benign	0.13	T
Sift4G	Benign	0.55	T
PromoterAI		0.036	Neutral
Varity_R		0.17
gMVP		0.17
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

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

Other links and lift over

hg19: chr12-120972696;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar