rs10242

chr10-15103949-T-Cchr10-15103949-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_183005.5(RPP38):c.635T>C(p.Ile212Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,614,070 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.024 (65 hom., cov: 32)
  • Exomes 𝑓: 0.027 (566 hom.)
• Consequence: RPP38 NM_183005.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

Genes affected

RPP38 (HGNC:30329): (ribonuclease P/MRP subunit p38) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Located in fibrillar center. Part of multimeric ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

NMT2 (HGNC:7858): (N-myristoyltransferase 2) This gene encodes one of two N-myristoyltransferase proteins. N-terminal myristoylation is a lipid modification that is involved in regulating the function and localization of signaling proteins. The encoded protein catalyzes the addition of a myristoyl group to the N-terminal glycine residue of many signaling proteins, including the human immunodeficiency virus type 1 (HIV-1) proteins, Gag and Nef. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020759702).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0235 (3579/152258) while in subpopulation AMR AF= 0.0333 (509/15288). AF 95% confidence interval is 0.0309. There are 65 homozygotes in gnomad4. There are 1794 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3577 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPP38	NM_183005.5	c.635T>C	p.Ile212Thr	missense_variant	3/3	ENST00000378197.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPP38	ENST00000378197.5	c.635T>C	p.Ile212Thr	missense_variant	3/3	1	NM_183005.5	P1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3577 AN: 152140 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0252 AC: 6323 AN: 251388 Hom.: 93 AF XY: 0.0249 AC XY: 3384 AN XY: 135874

Gnomad AFR exome AF: 0.00418

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00764

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0364

GnomAD4 exome AF: 0.0271 AC: 39608 AN: 1461812 Hom.: 566 Cov.: 34 AF XY: 0.0267 AC XY: 19439 AN XY: 727222

Gnomad4 AFR exome AF: 0.00571

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0291

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00868

Gnomad4 FIN exome AF: 0.0463

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0259

GnomAD4 genome AF: 0.0235 AC: 3579 AN: 152258 Hom.: 65 Cov.: 32 AF XY: 0.0241 AC XY: 1794 AN XY: 74426

Gnomad4 AFR AF: 0.00570

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0292 Hom.: 194

Bravo AF: 0.0210

TwinsUK AF: 0.0343 AC: 127

ALSPAC AF: 0.0327 AC: 126

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.0287 AC: 247

ExAC AF: 0.0251 AC: 3046

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0357

EpiControl AF: 0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.010
Dann	Benign	0.49
DEOGEN2	Benign	0.0026	T;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
MetaRNN	Benign	0.0021	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.065	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.35	N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.85	T;.;T;T
Sift4G	Benign	0.72	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.023
MPC		0.11
ClinPred		0.0051	T
GERP RS		-5.2
Varity_R		0.041
gMVP		0.17

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: rs10242; hg19: chr10-15145948;