7-40133198-T-C

Position:

• chr7-40133198-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138701.4(MPLKIP):​c.401A>G​(p.Asn134Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MPLKIP NM_138701.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

MPLKIP (HGNC:16002): (M-phase specific PLK1 interacting protein) The protein encoded by this gene localizes to the centrosome during mitosis and to the midbody during cytokinesis. The protein is phosphorylated by cyclin-dependent kinase 1 during mitosis and subsequently interacts with polo-like kinase 1. The protein is thought to function in regulating mitosis and cytokinesis. Mutations in this gene result in nonphotosensitive trichothiodystrophy. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37014252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPLKIP	NM_138701.4	c.401A>G	p.Asn134Ser	missense_variant	2/2	ENST00000306984.8	NP_619646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPLKIP	ENST00000306984.8	c.401A>G	p.Asn134Ser	missense_variant	2/2	1	NM_138701.4	ENSP00000304553.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 134 of the MPLKIP protein (p.Asn134Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MPLKIP-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	N;.
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.21	T;.
Polyphen		0.99	D;D
Vest4		0.41
MutPred		0.14		Gain of phosphorylation at N134 (P = 0.0051);Gain of phosphorylation at N134 (P = 0.0051);
MVP		0.78
MPC		0.83
ClinPred		0.94	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.36
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr7-40172797; COSMIC: COSV99999032; COSMIC: COSV99999032;