chr16-82151507-T-G

Variant names:

• chr16-82151507-T-G
• rs2303267
• NM_005792.2:c.172A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005792.2(MPHOSPH6):​c.172A>C​(p.Ile58Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,433,040 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MPHOSPH6 NM_005792.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH6	NM_005792.2	MANE Select	c.172A>C	p.Ile58Leu	missense	Exon 3 of 5	NP_005783.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH6	ENST00000258169.9	TSL:1 MANE Select	c.172A>C	p.Ile58Leu	missense	Exon 3 of 5	ENSP00000258169.4
	MPHOSPH6	ENST00000563504.5	TSL:2	c.85A>C	p.Ile29Leu	missense	Exon 3 of 5	ENSP00000456626.1
	MPHOSPH6	ENST00000563100.5	TSL:5	n.118A>C		non_coding_transcript_exon	Exon 4 of 7	ENSP00000454996.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433040 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 711174

African (AFR) AF: 0.00 AC: 0 AN: 32094

American (AMR) AF: 0.0000255 AC: 1 AN: 39186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39334

South Asian (SAS) AF: 0.00 AC: 0 AN: 80010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100394

Other (OTH) AF: 0.00 AC: 0 AN: 59090

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.22
Sift	Benign	0.046	D
Sift4G	Benign	0.30	T
Polyphen		0.96	D
Vest4		0.68
MutPred		0.72		Loss of sheet (P = 0.0228)
MVP		0.36
MPC		0.0047
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.71
gMVP		0.29

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: rs2303267; hg19: chr16-82185112;