rs755352806

Variant names:

• chr6-4999818-T-A
• rs755352806
• NM_006638.4:c.424A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-4999818-T-A
• chr6-4999818-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006638.4(RPP40):​c.424A>T​(p.Met142Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M142V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPP40 NM_006638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32432145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006638.4. 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
	RPP40	NM_006638.4	MANE Select	c.424A>T	p.Met142Leu	missense	Exon 4 of 8	NP_006629.2	O75818-1
	RPP40	NM_001286132.2		c.355A>T	p.Met119Leu	missense	Exon 3 of 7	NP_001273061.1	O75818-2
	RPP40	NM_001286133.2		c.424A>T	p.Met142Leu	missense	Exon 4 of 7	NP_001273062.1	A0A087X1N3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP40	ENST00000380051.7	TSL:5 MANE Select	c.424A>T	p.Met142Leu	missense	Exon 4 of 8	ENSP00000369391.2	O75818-1
	RPP40	ENST00000319533.9	TSL:1	c.355A>T	p.Met119Leu	missense	Exon 3 of 7	ENSP00000317998.5	O75818-2
	RPP40	ENST00000618533.4	TSL:5	c.424A>T	p.Met142Leu	missense	Exon 4 of 7	ENSP00000484334.1	A0A087X1N3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.58
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.40	T
Sift4G	Benign	1.0	T
Polyphen		0.0090	B
Vest4		0.25
MutPred		0.75		Gain of ubiquitination at K143 (P = 0.0719)
MVP		0.21
MPC		0.19
ClinPred		0.52	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.28
Mutation Taster		=78/22	polymorphism

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: rs755352806; hg19: chr6-5000052;