12-120534893-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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 was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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

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]

ENSG00000288623 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2722813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF10	NM_014868.5	c.82T>A	p.Ser28Thr	missense_variant	Exon 1 of 17	ENST00000325954.9	NP_055683.3
RNF10	NM_001330474.2	c.82T>A	p.Ser28Thr	missense_variant	Exon 1 of 17		NP_001317403.1
LOC128071547	NM_001414895.1	c.197T>A	p.Phe66Tyr	missense_variant	Exon 1 of 1		NP_001401824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF10	ENST00000325954.9	c.82T>A	p.Ser28Thr	missense_variant	Exon 1 of 17	1	NM_014868.5	ENSP00000322242.4
ENSG00000288623	ENST00000675818.1	c.197T>A	p.Phe66Tyr	missense_variant	Exon 1 of 1			ENSP00000502390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82T>A (p.S28T) alteration is located in exon 1 (coding exon 1) of the RNF10 gene. This alteration results from a T to A substitution at nucleotide position 82, causing the serine (S) at amino acid position 28 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.64	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.13	T;D;T
Sift4G	Benign	0.55	T;D;T
Polyphen		0.25	B;.;.
Vest4		0.19
MutPred		0.23		Loss of phosphorylation at S28 (P = 0.0692);Loss of phosphorylation at S28 (P = 0.0692);Loss of phosphorylation at S28 (P = 0.0692);
MVP		0.66
MPC		0.36
ClinPred		0.34	T
GERP RS		3.8
Varity_R		0.17
gMVP		0.17

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-120972696;