13-19647025-A-G

Variant names:

• chr13-19647025-A-G
• rs141397171
• NM_017520.4:c.952A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017520.4(MPHOSPH8):​c.952A>G​(p.Met318Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. M318L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPHOSPH8 NM_017520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0498026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH8	NM_017520.4	c.952A>G	p.Met318Val	missense_variant	Exon 3 of 14	ENST00000361479.10	NP_059990.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPHOSPH8	ENST00000361479.10	c.952A>G	p.Met318Val	missense_variant	Exon 3 of 14	1	NM_017520.4	ENSP00000355388.4
MPHOSPH8	ENST00000414242.3	c.271A>G	p.Met91Val	missense_variant	Exon 1 of 3	1		ENSP00000414663.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.019
DANN	Benign	0.34
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.35		Loss of loop (P = 0.0203);
MVP		0.23
MPC		0.24
ClinPred		0.033	T
GERP RS		-5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.019
gMVP		0.016

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

LitVar

Other links and lift over

dbSNP: rs141397171; hg19: chr13-20221165;