12-120534876-A-G

Variant names:

• chr12-120534876-A-G
• NM_014868.5:c.65A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_014868.5(RNF10):​c.65A>G​(p.Asn22Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09
• 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]

ENSG00000288623 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10005766).
• BP6: Variant 12-120534876-A-G is Benign according to our data. Variant chr12-120534876-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2534525.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF10	NM_014868.5	c.65A>G	p.Asn22Ser	missense_variant	Exon 1 of 17	ENST00000325954.9	NP_055683.3
RNF10	NM_001330474.2	c.65A>G	p.Asn22Ser	missense_variant	Exon 1 of 17		NP_001317403.1
LOC128071547	NM_001414895.1	c.180A>G	p.Gln60Gln	synonymous_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.65A>G	p.Asn22Ser	missense_variant	Exon 1 of 17	1	NM_014868.5	ENSP00000322242.4
ENSG00000288623	ENST00000675818.1	c.180A>G	p.Gln60Gln	synonymous_variant	Exon 1 of 1			ENSP00000502390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.6
DANN	Benign	0.52
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.34	N;.;N
PhyloP100		1.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.33	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.062
MutPred		0.27		Gain of phosphorylation at N22 (P = 6e-04);Gain of phosphorylation at N22 (P = 6e-04);Gain of phosphorylation at N22 (P = 6e-04);
MVP		0.47
MPC		0.15
ClinPred		0.20	T
GERP RS		1.8
PromoterAI		-0.051	Neutral
Varity_R		0.041
gMVP		0.092
Mutation Taster		=86/14	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

hg19: chr12-120972679;