16-82151507-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I58V) has been classified as Likely benign.

• 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH6	NM_005792.2	c.172A>C	p.Ile58Leu	missense_variant	Exon 3 of 5	ENST00000258169.9	NP_005783.2
MPHOSPH6	XM_011522808.4	c.118A>C	p.Ile40Leu	missense_variant	Exon 4 of 6		XP_011521110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPHOSPH6	ENST00000258169.9	c.172A>C	p.Ile58Leu	missense_variant	Exon 3 of 5	1	NM_005792.2	ENSP00000258169.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.22
Sift	Benign	0.046	D;T
Sift4G	Benign	0.30	T;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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-82185112;