13-19647187-G-T

Variant names:

• chr13-19647187-G-T
• NM_017520.4:c.1114G>T

Variant summary

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

The NM_017520.4(MPHOSPH8):​c.1114G>T​(p.Ala372Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPHOSPH8 NM_017520.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.290

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=0.03398791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH8	NM_017520.4	c.1114G>T	p.Ala372Ser	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.1114G>T	p.Ala372Ser	missense_variant	Exon 3 of 14	1	NM_017520.4	ENSP00000355388.4
MPHOSPH8	ENST00000414242.3	c.433G>T	p.Ala145Ser	missense_variant	Exon 1 of 3	1		ENSP00000414663.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1114G>T (p.A372S) alteration is located in exon 3 (coding exon 3) of the MPHOSPH8 gene. This alteration results from a G to T substitution at nucleotide position 1114, causing the alanine (A) at amino acid position 372 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.33
DANN	Benign	0.25
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.025
Sift	Benign	0.96	T
Sift4G	Benign	0.53	T
Polyphen		0.0010	B
Vest4		0.081
MutPred		0.17		Gain of phosphorylation at A372 (P = 0.0111);
MVP		0.50
MPC		0.22
ClinPred		0.035	T
GERP RS		-8.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.015

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: chr13-20221327;