10-97366615-C-A

Position:

• chr10-97366615-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015179.4(RRP12):​c.3222G>T​(p.Glu1074Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RRP12 NM_015179.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0710

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17816845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP12	NM_015179.4	c.3222G>T	p.Glu1074Asp	missense_variant	28/34	ENST00000370992.9	NP_055994.2
RRP12	NM_001145114.1	c.3039G>T	p.Glu1013Asp	missense_variant	26/32		NP_001138586.1
RRP12	NM_001284337.2	c.2922G>T	p.Glu974Asp	missense_variant	25/31		NP_001271266.1
RRP12	XM_047424903.1	c.3138G>T	p.Glu1046Asp	missense_variant	27/33		XP_047280859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP12	ENST00000370992.9	c.3222G>T	p.Glu1074Asp	missense_variant	28/34	1	NM_015179.4	ENSP00000360031	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Jan 23, 2023

The c.3222G>T (p.E1074D) alteration is located in exon 28 (coding exon 28) of the RRP12 gene. This alteration results from a G to T substitution at nucleotide position 3222, causing the glutamic acid (E) at amino acid position 1074 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	0.31
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;.;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	.;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.089	.;T;D;D
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.70	P;B;P;.
Vest4		0.30
MutPred		0.31		Loss of helix (P = 0.028);.;Loss of helix (P = 0.028);.;
MVP		0.36
MPC		0.20
ClinPred		0.81	D
GERP RS		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.14

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: chr10-99126372;