rs757494047

Variant names:

• chr13-19647250-G-A
• rs757494047
• NM_017520.4:c.1177G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-19647250-G-A
• chr13-19647250-G-C
• chr13-19647250-G-T

Variant summary

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

The NM_017520.4(MPHOSPH8):​c.1177G>A​(p.Gly393Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,611,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: MPHOSPH8 NM_017520.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.339
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06279811).

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.1177G>A	p.Gly393Arg	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.1177G>A	p.Gly393Arg	missense	Exon 3 of 14	ENSP00000355388.4	Q99549-1
	MPHOSPH8	ENST00000414242.3	TSL:1	c.496G>A	p.Gly166Arg	missense	Exon 1 of 3	ENSP00000414663.3	A0A0A0MT47
	MPHOSPH8	ENST00000971230.1		c.1177G>A	p.Gly393Arg	missense	Exon 3 of 15	ENSP00000641289.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000813 AC: 20 AN: 246132 AF XY: 0.0000749

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000239

Gnomad ASJ exome AF: 0.000409

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000514 AC: 75 AN: 1458682 Hom.: 0 Cov.: 32 AF XY: 0.0000592 AC XY: 43 AN XY: 725810

African (AFR) AF: 0.0000303 AC: 1 AN: 33016

American (AMR) AF: 0.000366 AC: 16 AN: 43738

Ashkenazi Jewish (ASJ) AF: 0.000424 AC: 11 AN: 25970

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.000244 AC: 21 AN: 85890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111130

Other (OTH) AF: 0.0000665 AC: 4 AN: 60144

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.000915 AC: 14 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000451 Hom.: 0

Bravo AF: 0.000253

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.5
DANN	Benign	0.76
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.34
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.063
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.83	P
Vest4		0.44
MutPred		0.22		Gain of MoRF binding (P = 0.0153)
MVP		0.37
MPC		0.53
ClinPred		0.026	T
GERP RS		2.6
PromoterAI		0.0050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.031
Mutation Taster		=97/3	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: rs757494047; hg19: chr13-20221390;