rs16956538

Variant names:

• chr16-82149368-T-C
• rs16956538
• NM_005792.2:c.291A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005792.2(MPHOSPH6):​c.291A>G​(p.Ala97Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 1,612,908 control chromosomes in the GnomAD database, including 388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (199 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (189 hom.)
• Consequence: MPHOSPH6 NM_005792.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.704

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-82149368-T-C is Benign according to our data. Variant chr16-82149368-T-C is described in ClinVar as [Benign]. Clinvar id is 777047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.704 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH6	NM_005792.2	c.291A>G	p.Ala97Ala	synonymous_variant	Exon 4 of 5	ENST00000258169.9	NP_005783.2
MPHOSPH6	XM_011522808.4	c.237A>G	p.Ala79Ala	synonymous_variant	Exon 5 of 6		XP_011521110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPHOSPH6	ENST00000258169.9	c.291A>G	p.Ala97Ala	synonymous_variant	Exon 4 of 5	1	NM_005792.2	ENSP00000258169.4
MPHOSPH6	ENST00000563504.5	c.204A>G	p.Ala68Ala	synonymous_variant	Exon 4 of 5	2		ENSP00000456626.1
MPHOSPH6	ENST00000563100.5	n.237A>G		non_coding_transcript_exon_variant	Exon 5 of 7	5		ENSP00000454996.1
MPHOSPH6	ENST00000568016.1	n.*112A>G		downstream_gene_variant		5		ENSP00000457537.1

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4292 AN: 152232 Hom.: 198 Cov.: 33

Gnomad AFR AF: 0.0978

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00686 AC: 1719 AN: 250434 Hom.: 69 AF XY: 0.00474 AC XY: 642 AN XY: 135434

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000387

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00288 AC: 4202 AN: 1460558 Hom.: 189 Cov.: 32 AF XY: 0.00255 AC XY: 1854 AN XY: 726682

Gnomad4 AFR exome AF: 0.0986

Gnomad4 AMR exome AF: 0.00436

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000203

Gnomad4 OTH exome AF: 0.00681

GnomAD4 genome AF: 0.0282 AC: 4297 AN: 152350 Hom.: 199 Cov.: 33 AF XY: 0.0266 AC XY: 1979 AN XY: 74506

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0133 Hom.: 47

Bravo AF: 0.0316

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16956538; hg19: chr16-82182973;