6-4996308-G-A

Variant names:

• chr6-4996308-G-A
• rs1759380758
• NM_006638.4:c.672C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006638.4(RPP40):​c.672C>T​(p.Ser224Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPP40 NM_006638.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.582 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP40	NM_006638.4	c.672C>T	p.Ser224Ser	synonymous_variant	Exon 6 of 8	ENST00000380051.7	NP_006629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP40	ENST00000380051.7	c.672C>T	p.Ser224Ser	synonymous_variant	Exon 6 of 8	5	NM_006638.4	ENSP00000369391.2
RPP40	ENST00000319533.9	c.603C>T	p.Ser201Ser	synonymous_variant	Exon 5 of 7	1		ENSP00000317998.5
RPP40	ENST00000618533.4	c.546C>T	p.Ser182Ser	synonymous_variant	Exon 5 of 7	5		ENSP00000484334.1
RPP40	ENST00000464646.1	c.492C>T	p.Ser164Ser	synonymous_variant	Exon 6 of 8	5		ENSP00000419431.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.50

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: rs1759380758; hg19: chr6-4996542;