rs199946178

Variant names:

• chr6-5003915-G-A
• rs199946178
• NM_006638.4:c.88C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-5003915-G-A
• chr6-5003915-G-C
• chr6-5003915-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006638.4(RPP40):​c.88C>T​(p.Arg30Trp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPP40 NM_006638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

RPP40 (HGNC:20992): (ribonuclease P/MRP subunit p40) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Part of multimeric ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

LYRM4-AS1 (HGNC:52055): (LYRM4 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28170675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP40	NM_006638.4	c.88C>T	p.Arg30Trp	missense_variant	Exon 1 of 8	ENST00000380051.7	NP_006629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP40	ENST00000380051.7	c.88C>T	p.Arg30Trp	missense_variant	Exon 1 of 8	5	NM_006638.4	ENSP00000369391.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461440 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727048

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.;T
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.012	D;D;.
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.96	D;D;.
Vest4		0.24
MutPred		0.34		Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);Loss of sheet (P = 0.0063);
MVP		0.62
MPC		0.60
ClinPred		0.65	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.49

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: rs199946178; hg19: chr6-5004149; COSMIC: COSV60292586; COSMIC: COSV60292586;