NM_183005.5:c.635T>C

Variant names:

• chr10-15103949-T-C
• rs10242
• NM_183005.5:c.635T>C

Variant summary

Our verdict is Benign. The variant received -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. 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: 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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3579 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183005.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP38	NM_183005.5	MANE Select	c.635T>C	p.Ile212Thr	missense	Exon 3 of 3	NP_892117.1
	RPP38	NM_001097590.3		c.635T>C	p.Ile212Thr	missense	Exon 3 of 3	NP_001091059.1
	RPP38	NM_001265601.2		c.635T>C	p.Ile212Thr	missense	Exon 2 of 2	NP_001252530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP38	ENST00000378197.5	TSL:1 MANE Select	c.635T>C	p.Ile212Thr	missense	Exon 3 of 3	ENSP00000367439.4
	RPP38	ENST00000378202.5	TSL:1	c.635T>C	p.Ile212Thr	missense	Exon 2 of 2	ENSP00000367444.5
	NMT2	ENST00000466201.1	TSL:1	n.128-266A>G		intron	N/A

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

GnomAD2 exomes AF: 0.0252 AC: 6323 AN: 251388 AF XY: 0.0249

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 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

African (AFR) AF: 0.00571 AC: 191 AN: 33462

American (AMR) AF: 0.0226 AC: 1010 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 760 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00868 AC: 749 AN: 86256

European-Finnish (FIN) AF: 0.0463 AC: 2472 AN: 53418

Middle Eastern (MID) AF: 0.0499 AC: 288 AN: 5768

European-Non Finnish (NFE) AF: 0.0293 AC: 32571 AN: 1111976

Other (OTH) AF: 0.0259 AC: 1564 AN: 60394

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

African (AFR) AF: 0.00570 AC: 237 AN: 41568

American (AMR) AF: 0.0333 AC: 509 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4826

European-Finnish (FIN) AF: 0.0485 AC: 514 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0306 AC: 2080 AN: 68012

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0281 Hom.: 248

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 v4.9

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
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.065	N
PhyloP100		0.0010
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.11
Sift	Benign	0.85	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.11
ClinPred		0.0051	T
GERP RS		-5.2
Varity_R		0.041
gMVP		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs10242; hg19: chr10-15145948; COSMIC: COSV107484925;