chr16-82149364-C-T

Variant names:

• chr16-82149364-C-T
• rs768439916
• NM_005792.2:c.295G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005792.2(MPHOSPH6):​c.295G>A​(p.Glu99Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,460,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000029 (1 hom.)
• Consequence: MPHOSPH6 NM_005792.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.067996174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005792.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH6	NM_005792.2	MANE Select	c.295G>A	p.Glu99Lys	missense	Exon 4 of 5	NP_005783.2	Q99547

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH6	ENST00000258169.9	TSL:1 MANE Select	c.295G>A	p.Glu99Lys	missense	Exon 4 of 5	ENSP00000258169.4	Q99547
	MPHOSPH6	ENST00000953188.1		c.325G>A	p.Glu109Lys	missense	Exon 4 of 5	ENSP00000623247.1
	MPHOSPH6	ENST00000880962.1		c.313G>A	p.Glu105Lys	missense	Exon 4 of 5	ENSP00000551021.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000559 AC: 14 AN: 250512 AF XY: 0.0000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1460664 Hom.: 1 Cov.: 32 AF XY: 0.0000427 AC XY: 31 AN XY: 726736

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.0000331 AC: 2 AN: 60388

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.76
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.095	N
PhyloP100		1.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.051
Sift	Benign	0.40	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.44		Gain of ubiquitination at E99 (P = 0.0109)
MVP		0.34
MPC		0.0017
ClinPred		0.062	T
GERP RS		4.7
Varity_R		0.14
gMVP		0.15
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs768439916; hg19: chr16-82182969; COSMIC: COSV50737425; COSMIC: COSV50737425;