rs2297988

Variant names:

• chr10-97358625-T-C
• rs2297988
• NM_015179.4:c.3709-6A>G

Variant summary

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

The NM_015179.4(RRP12):​c.3709-6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,606,020 control chromosomes in the GnomAD database, including 95,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (13108 hom., cov: 30)
  • Exomes 𝑓: 0.33 (82013 hom.)
• Consequence: RRP12 NM_015179.4 splice_region, intron
• Scores: Splicing: ADA: 0.000008779
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 30 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015179.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP12	NM_015179.4	MANE Select	c.3709-6A>G		splice_region intron	N/A	NP_055994.2	Q5JTH9-1
	RRP12	NM_001145114.1		c.3526-6A>G		splice_region intron	N/A	NP_001138586.1	Q5JTH9-3
	RRP12	NM_001284337.2		c.3409-6A>G		splice_region intron	N/A	NP_001271266.1	Q5JTH9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP12	ENST00000370992.9	TSL:1 MANE Select	c.3709-6A>G		splice_region intron	N/A	ENSP00000360031.4	Q5JTH9-1
	RRP12	ENST00000315563.10	TSL:1	c.3409-6A>G		splice_region intron	N/A	ENSP00000324315.6	Q5JTH9-2
	RRP12	ENST00000479481.5	TSL:1	n.2693-6A>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60721 AN: 151636 Hom.: 13076 Cov.: 30

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.387

GnomAD2 exomes AF: 0.342 AC: 85847 AN: 251342 AF XY: 0.340

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.298

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.331 AC: 481150 AN: 1454264 Hom.: 82013 Cov.: 31 AF XY: 0.331 AC XY: 239900 AN XY: 723774

African (AFR) AF: 0.580 AC: 19307 AN: 33266

American (AMR) AF: 0.309 AC: 13799 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 9526 AN: 26090

East Asian (EAS) AF: 0.286 AC: 11329 AN: 39676

South Asian (SAS) AF: 0.353 AC: 30411 AN: 86100

European-Finnish (FIN) AF: 0.351 AC: 18719 AN: 53330

Middle Eastern (MID) AF: 0.381 AC: 2192 AN: 5754

European-Non Finnish (NFE) AF: 0.321 AC: 354799 AN: 1105254

Other (OTH) AF: 0.351 AC: 21068 AN: 60086

GnomAD4 genome AF: 0.401 AC: 60809 AN: 151756 Hom.: 13108 Cov.: 30 AF XY: 0.402 AC XY: 29796 AN XY: 74166

African (AFR) AF: 0.569 AC: 23547 AN: 41386

American (AMR) AF: 0.369 AC: 5610 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1288 AN: 3468

East Asian (EAS) AF: 0.300 AC: 1538 AN: 5132

South Asian (SAS) AF: 0.368 AC: 1767 AN: 4796

European-Finnish (FIN) AF: 0.366 AC: 3857 AN: 10528

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21906 AN: 67910

Other (OTH) AF: 0.389 AC: 821 AN: 2112

Alfa AF: 0.347 Hom.: 8275

Bravo AF: 0.406

Asia WGS AF: 0.364 AC: 1269 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.49
PhyloP100		0.23
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000088
SpliceAI score (max)		0.090		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: rs2297988; hg19: chr10-99118382; COSMIC: COSV59668229;