rs2275580

Variant names:

• chr10-97366192-C-T
• rs2275580
• NM_015179.4:c.3433G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015179.4(RRP12):​c.3433G>A​(p.Gly1145Ser) variant causes a missense change. The variant allele was found at a frequency of 0.562 in 1,610,472 control chromosomes in the GnomAD database, including 261,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (18591 hom., cov: 29)
  • Exomes 𝑓: 0.57 (242954 hom.)
• Consequence: RRP12 NM_015179.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9788742E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRP12	NM_015179.4	c.3433G>A	p.Gly1145Ser	missense_variant	Exon 29 of 34	ENST00000370992.9	NP_055994.2
RRP12	NM_001145114.1	c.3250G>A	p.Gly1084Ser	missense_variant	Exon 27 of 32		NP_001138586.1
RRP12	NM_001284337.2	c.3133G>A	p.Gly1045Ser	missense_variant	Exon 26 of 31		NP_001271266.1
RRP12	XM_047424903.1	c.3349G>A	p.Gly1117Ser	missense_variant	Exon 28 of 33		XP_047280859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP12	ENST00000370992.9	c.3433G>A	p.Gly1145Ser	missense_variant	Exon 29 of 34	1	NM_015179.4	ENSP00000360031.4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70406 AN: 151346 Hom.: 18595 Cov.: 29

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.499

GnomAD2 exomes AF: 0.538 AC: 134388 AN: 249570 AF XY: 0.542

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.427

Gnomad FIN exome AF: 0.554

Gnomad NFE exome AF: 0.597

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.572 AC: 834076 AN: 1459008 Hom.: 242954 Cov.: 60 AF XY: 0.570 AC XY: 413884 AN XY: 725928

African (AFR) AF: 0.186 AC: 6212 AN: 33480

American (AMR) AF: 0.590 AC: 26381 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 14406 AN: 26136

East Asian (EAS) AF: 0.412 AC: 16349 AN: 39698

South Asian (SAS) AF: 0.487 AC: 41966 AN: 86254

European-Finnish (FIN) AF: 0.556 AC: 28154 AN: 50642

Middle Eastern (MID) AF: 0.524 AC: 3020 AN: 5766

European-Non Finnish (NFE) AF: 0.598 AC: 665190 AN: 1111948

Other (OTH) AF: 0.537 AC: 32398 AN: 60370

GnomAD4 genome AF: 0.465 AC: 70407 AN: 151464 Hom.: 18591 Cov.: 29 AF XY: 0.464 AC XY: 34302 AN XY: 73928

African (AFR) AF: 0.200 AC: 8268 AN: 41318

American (AMR) AF: 0.537 AC: 8132 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1881 AN: 3462

East Asian (EAS) AF: 0.419 AC: 2153 AN: 5134

South Asian (SAS) AF: 0.472 AC: 2251 AN: 4768

European-Finnish (FIN) AF: 0.544 AC: 5691 AN: 10462

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40348 AN: 67872

Other (OTH) AF: 0.498 AC: 1042 AN: 2092

Alfa AF: 0.549 Hom.: 78059

Bravo AF: 0.453

TwinsUK AF: 0.584 AC: 2167

ALSPAC AF: 0.604 AC: 2329

ESP6500AA AF: 0.211 AC: 928

ESP6500EA AF: 0.597 AC: 5136

ExAC AF: 0.534 AC: 64827

Asia WGS AF: 0.424 AC: 1473 AN: 3478

EpiCase AF: 0.593

EpiControl AF: 0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.;T;.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D;D;D;D
MetaRNN	Benign	0.00020	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M;.;M;.;.
PhyloP100		5.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	.;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.13	.;T;T;T;.
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.94	P;B;P;.;.
Vest4		0.15
MPC		0.29
ClinPred		0.029	T
GERP RS		4.3
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.11
Mutation Taster		=82/18	polymorphism (auto)

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: rs2275580; hg19: chr10-99125949; COSMIC: COSV59667805; COSMIC: COSV59667805;