NM_017520.4:c.906G>T

Variant names:

• chr13-19646979-G-T
• rs376037584
• NM_017520.4:c.906G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017520.4(MPHOSPH8):​c.906G>T​(p.Gln302His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,594,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q302Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MPHOSPH8 NM_017520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 1 publications found

Genes affected

MPHOSPH8 (HGNC:29810): (M-phase phosphoprotein 8) Enables chromatin binding activity and methylated histone binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; regulation of DNA methylation; and regulation of gene expression. Located in several cellular components, including cytosol; heterochromatin; and nuclear lumen. Part of nucleosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06582412).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017520.4. 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
	MPHOSPH8	NM_017520.4	MANE Select	c.906G>T	p.Gln302His	missense	Exon 3 of 14	NP_059990.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH8	ENST00000361479.10	TSL:1 MANE Select	c.906G>T	p.Gln302His	missense	Exon 3 of 14	ENSP00000355388.4	Q99549-1
	MPHOSPH8	ENST00000414242.3	TSL:1	c.225G>T	p.Gln75His	missense	Exon 1 of 3	ENSP00000414663.3	A0A0A0MT47
	MPHOSPH8	ENST00000971230.1		c.906G>T	p.Gln302His	missense	Exon 3 of 15	ENSP00000641289.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000432 AC: 1 AN: 231296 AF XY: 0.00

Gnomad AFR exome AF: 0.0000632

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: 6.93e-7 AC: 1 AN: 1442194 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717402

African (AFR) AF: 0.0000314 AC: 1 AN: 31864

American (AMR) AF: 0.00 AC: 0 AN: 38326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 82604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106874

Other (OTH) AF: 0.00 AC: 0 AN: 59330

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.0000242 AC: 1 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.0
DANN	Benign	0.94
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.26
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.062
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.039	D
Polyphen		0.056	B
Vest4		0.20
MutPred		0.18		Gain of catalytic residue at M304 (P = 0.0427)
MVP		0.25
MPC		0.45
ClinPred		0.072	T
GERP RS		-5.0
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.082
gMVP		0.024
Mutation Taster		=89/11	polymorphism

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: rs376037584; hg19: chr13-20221119;