10-97360562-T-C

Position:

• chr10-97360562-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015179.4(RRP12):​c.3624A>G​(p.Ile1208Met) 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. 15/21 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: RRP12 NM_015179.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.275

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025697619).
• BP6: Variant 10-97360562-T-C is Benign according to our data. Variant chr10-97360562-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3156499.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP12	NM_015179.4	c.3624A>G	p.Ile1208Met	missense_variant	31/34	ENST00000370992.9	NP_055994.2
RRP12	NM_001145114.1	c.3441A>G	p.Ile1147Met	missense_variant	29/32		NP_001138586.1
RRP12	NM_001284337.2	c.3324A>G	p.Ile1108Met	missense_variant	28/31		NP_001271266.1
RRP12	XM_047424903.1	c.3540A>G	p.Ile1180Met	missense_variant	30/33		XP_047280859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP12	ENST00000370992.9	c.3624A>G	p.Ile1208Met	missense_variant	31/34	1	NM_015179.4	ENSP00000360031	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

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	0.048
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.011	T;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.50	.;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.026	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.29	.;N;N;N
REVEL	Benign	0.013
Sift	Benign	0.11	.;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.12
MutPred		0.23		Loss of catalytic residue at P1210 (P = 0.0535);.;Loss of catalytic residue at P1210 (P = 0.0535);.;
MVP		0.19
MPC		0.16
ClinPred		0.030	T
GERP RS		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.036

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: rs1589408349; hg19: chr10-99120319; COSMIC: COSV59667382;