NM_006638.4:c.250A>G

Variant names:

• chr6-5002119-T-C
• NM_006638.4:c.250A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006638.4(RPP40):​c.250A>G​(p.Ser84Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: RPP40 NM_006638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13092944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP40	NM_006638.4	c.250A>G	p.Ser84Gly	missense_variant	Exon 2 of 8	ENST00000380051.7	NP_006629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP40	ENST00000380051.7	c.250A>G	p.Ser84Gly	missense_variant	Exon 2 of 8	5	NM_006638.4	ENSP00000369391.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460830 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.067
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0098	T;.;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.7	N;N;.;N
REVEL	Benign	0.047
Sift	Benign	0.18	T;T;.;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.014	B;B;.;.
Vest4		0.14
MutPred		0.58		Loss of glycosylation at S84 (P = 0.025);Loss of glycosylation at S84 (P = 0.025);Loss of glycosylation at S84 (P = 0.025);.;
MVP		0.27
MPC		0.21
ClinPred		0.076	T
GERP RS		3.0
Varity_R		0.077
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-5002353;