rs2303267

Positions:

• chr16-82151507-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005792.2(MPHOSPH6):​c.172A>G​(p.Ile58Val) variant causes a missense change. The variant allele was found at a frequency of 0.0311 in 1,585,124 control chromosomes in the GnomAD database, including 942 homozygotes. In-silico tool predicts 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 0.026 (82 hom., cov: 33)
  • Exomes 𝑓: 0.032 (860 hom.)
• Consequence: MPHOSPH6 NM_005792.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32

Genes affected

MPHOSPH6 (HGNC:7214): (M-phase phosphoprotein 6) Predicted to enable RNA binding activity. Involved in maturation of 5.8S rRNA. Located in cytosol; nucleolus; and nucleoplasm. Colocalizes with nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030200183).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH6	NM_005792.2	c.172A>G	p.Ile58Val	missense_variant	3/5	ENST00000258169.9
MPHOSPH6	XM_011522808.4	c.118A>G	p.Ile40Val	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH6	ENST00000258169.9	c.172A>G	p.Ile58Val	missense_variant	3/5	1	NM_005792.2	P1

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3960 AN: 152156 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0496

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.0253

GnomAD3 exomes AF: 0.0368 AC: 8536 AN: 232116 Hom.: 191 AF XY: 0.0375 AC XY: 4729 AN XY: 126014

Gnomad AFR exome AF: 0.00551

Gnomad AMR exome AF: 0.0466

Gnomad ASJ exome AF: 0.0319

Gnomad EAS exome AF: 0.0440

Gnomad SAS exome AF: 0.0562

Gnomad FIN exome AF: 0.0421

Gnomad NFE exome AF: 0.0322

Gnomad OTH exome AF: 0.0354

GnomAD4 exome AF: 0.0316 AC: 45273 AN: 1432850 Hom.: 860 Cov.: 30 AF XY: 0.0326 AC XY: 23161 AN XY: 711064

Gnomad4 AFR exome AF: 0.00436

Gnomad4 AMR exome AF: 0.0432

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.0550

Gnomad4 FIN exome AF: 0.0409

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0260 AC: 3964 AN: 152274 Hom.: 82 Cov.: 33 AF XY: 0.0271 AC XY: 2020 AN XY: 74448

Gnomad4 AFR AF: 0.00611

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0497

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0313

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0296 Hom.: 153

Bravo AF: 0.0234

TwinsUK AF: 0.0256 AC: 95

ALSPAC AF: 0.0296 AC: 114

ESP6500AA AF: 0.00705 AC: 31

ESP6500EA AF: 0.0313 AC: 268

ExAC AF: 0.0370 AC: 4494

Asia WGS AF: 0.0540 AC: 186 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0056	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;D
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.10
Sift	Benign	0.17	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.91	P;.
Vest4		0.43
MPC		0.0055
ClinPred		0.031	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.24

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: rs2303267; hg19: chr16-82185112; COSMIC: COSV50737498;