21-43797678-T-G

Variant names:

• chr21-43797678-T-G
• rs2838378
• NM_003683.6:c.600T>G

Variant summary

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

The NM_003683.6(RRP1):​c.600T>G​(p.Ile200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RRP1 NM_003683.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

Genes affected

RRP1 (HGNC:18785): (ribosomal RNA processing 1) The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRP1	NM_003683.6	c.600T>G	p.Ile200Met	missense_variant	Exon 7 of 13	ENST00000497547.2	NP_003674.1
RRP1	XM_017028485.3	c.600T>G	p.Ile200Met	missense_variant	Exon 7 of 13		XP_016883974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000497547.2	c.600T>G	p.Ile200Met	missense_variant	Exon 7 of 13	1	NM_003683.6	ENSP00000417464.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461698 Hom.: 0 Cov.: 56 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.40
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.24
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.78		Loss of MoRF binding (P = 0.1363);
MVP		0.12
MPC		0.39
ClinPred		0.87	D
GERP RS		-7.3
Varity_R		0.74
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2838378; hg19: chr21-45217559;