NM_014868.5:c.31A>G

Variant names:

• chr12-120534842-A-G
• rs747471809
• NM_014868.5:c.31A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014868.5(RNF10):​c.31A>G​(p.Thr11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,602,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 1 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):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.07639891).

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.31A>G	p.Thr11Ala	missense	Exon 1 of 17	NP_055683.3
	LOC128071547	NM_001414895.1	MANE Select	c.146A>G	p.His49Arg	missense	Exon 1 of 1	NP_001401824.1
	RNF10	NM_001330474.2		c.31A>G	p.Thr11Ala	missense	Exon 1 of 17	NP_001317403.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF10	ENST00000325954.9	TSL:1 MANE Select	c.31A>G	p.Thr11Ala	missense	Exon 1 of 17	ENSP00000322242.4
	ENSG00000288623	ENST00000675818.1	MANE Select	c.146A>G	p.His49Arg	missense	Exon 1 of 1	ENSP00000502390.1
	RNF10	ENST00000413266.6	TSL:5	c.31A>G	p.Thr11Ala	missense	Exon 1 of 17	ENSP00000415682.2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151932 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000660 AC: 15 AN: 227382 AF XY: 0.0000398

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000448

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1450914 Hom.: 0 Cov.: 31 AF XY: 0.00000831 AC XY: 6 AN XY: 721904

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.000384 AC: 17 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00 AC: 0 AN: 85666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110458

Other (OTH) AF: 0.00 AC: 0 AN: 60074

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151932 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74214

African (AFR) AF: 0.00 AC: 0 AN: 41344

American (AMR) AF: 0.000590 AC: 9 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions as Germline

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	0.053
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	-0.41	N
PhyloP100		1.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.52	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.019	D
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.18		Loss of loop (P = 0.0073)
MVP		0.61
MPC		0.19
ClinPred		0.023	T
GERP RS		2.4
PromoterAI		-0.062	Neutral
Varity_R		0.048
gMVP		0.25
Mutation Taster		=95/5	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

dbSNP: rs747471809; hg19: chr12-120972645; COSMIC: COSV58044196; COSMIC: COSV58044196;