rs1056629

Positions:

• chr16-82148499-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.*232A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 433,450 control chromosomes in the GnomAD database, including 5,805 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.

• Frequency:
  • Genomes: 𝑓 0.14 (2245 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3560 hom.)
• Consequence: MPHOSPH6 NM_005792.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPHOSPH6	NM_005792.2	c.*232A>G		3_prime_UTR_variant	5/5	ENST00000258169.9	NP_005783.2
MPHOSPH6	XM_011522808.4	c.*232A>G		3_prime_UTR_variant	6/6		XP_011521110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPHOSPH6	ENST00000258169	c.*232A>G		3_prime_UTR_variant	5/5	1	NM_005792.2	ENSP00000258169.4
MPHOSPH6	ENST00000563100.5	n.*72+160A>G		intron_variant		5		ENSP00000454996.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21826 AN: 152034 Hom.: 2230 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.139 AC: 38971 AN: 281298 Hom.: 3560 Cov.: 5 AF XY: 0.139 AC XY: 19920 AN XY: 142956

Gnomad4 AFR exome AF: 0.0585

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.144 AC: 21865 AN: 152152 Hom.: 2245 Cov.: 32 AF XY: 0.152 AC XY: 11285 AN XY: 74376

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.148

Alfa AF: 0.130 Hom.: 1709

Bravo AF: 0.155

Asia WGS AF: 0.287 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.28
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs1056629; hg19: chr16-82182104;