chr10-97366588-C-G

Position:

• chr10-97366588-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000370992.9(RRP12):​c.3249G>C​(p.Glu1083Asp) 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. 14/21 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: RRP12 ENST00000370992.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.970

Genes affected

RRP12 (HGNC:29100): (ribosomal RNA processing 12 homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in cytosol; nucleolus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RRP12 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05810201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP12	NM_015179.4	c.3249G>C	p.Glu1083Asp	missense_variant	28/34	ENST00000370992.9	NP_055994.2
RRP12	NM_001145114.1	c.3066G>C	p.Glu1022Asp	missense_variant	26/32		NP_001138586.1
RRP12	NM_001284337.2	c.2949G>C	p.Glu983Asp	missense_variant	25/31		NP_001271266.1
RRP12	XM_047424903.1	c.3165G>C	p.Glu1055Asp	missense_variant	27/33		XP_047280859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP12	ENST00000370992.9	c.3249G>C	p.Glu1083Asp	missense_variant	28/34	1	NM_015179.4	ENSP00000360031.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2022

The c.3249G>C (p.E1083D) alteration is located in exon 28 (coding exon 28) of the RRP12 gene. This alteration results from a G to C substitution at nucleotide position 3249, causing the glutamic acid (E) at amino acid position 1083 to be replaced by an aspartic acid (D). 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	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.69	.;T;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N;.;N;.
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.60	.;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.16	.;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.025	B;B;B;.
Vest4		0.12
MutPred		0.14		Gain of helix (P = 0.1736);.;Gain of helix (P = 0.1736);.;
MVP		0.25
MPC		0.14
ClinPred		0.51	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.057

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

LitVar

Other links and lift over

dbSNP: rs926703016; hg19: chr10-99126345;