12-120562954-G-A

Variant names:

• chr12-120562954-G-A
• NM_014868.5:c.1138G>A

Variant summary

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

The NM_014868.5(RNF10):​c.1138G>A​(p.Glu380Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,768 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RNF10 NM_014868.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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]

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=0.3037898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF10	NM_014868.5	c.1138G>A	p.Glu380Lys	missense_variant	Exon 8 of 17	ENST00000325954.9	NP_055683.3
RNF10	NM_001330474.2	c.1138G>A	p.Glu380Lys	missense_variant	Exon 8 of 17		NP_001317403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF10	ENST00000325954.9	c.1138G>A	p.Glu380Lys	missense_variant	Exon 8 of 17	1	NM_014868.5	ENSP00000322242.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461768 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727180

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1138G>A (p.E380K) alteration is located in exon 8 (coding exon 8) of the RNF10 gene. This alteration results from a G to A substitution at nucleotide position 1138, causing the glutamic acid (E) at amino acid position 380 to be replaced by a lysine (K). 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	0.085
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;T;.
Eigen	Benign	-0.0011
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Uncertain	0.069	D
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.56
Sift	Benign	0.097	T;D;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.22	B;.;P
Vest4		0.32
MutPred		0.40		Gain of MoRF binding (P = 0.0065);.;Gain of MoRF binding (P = 0.0065);
MVP		0.90
MPC		0.22
ClinPred		0.56	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.38

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: chr12-121000757;