NM_138701.4:c.487C>A

Variant names:

• chr7-40133112-G-T
• NM_138701.4:c.487C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138701.4(MPLKIP):​c.487C>A​(p.Gln163Lys) 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. 16/22 in silico tools predict 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: 3.15
• Publications: 0 publications found

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]

MPLKIP Gene-Disease associations (from GenCC):

• trichothiodystrophy 4, nonphotosensitive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1294598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138701.4. 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
	MPLKIP	NM_138701.4	MANE Select	c.487C>A	p.Gln163Lys	missense	Exon 2 of 2	NP_619646.1	Q8TAP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPLKIP	ENST00000306984.8	TSL:1 MANE Select	c.487C>A	p.Gln163Lys	missense	Exon 2 of 2	ENSP00000304553.5	Q8TAP9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.20
Sift	Benign	0.18	T
Sift4G	Benign	1.0	T
Polyphen		0.046	B
Vest4		0.13
MutPred		0.28		Gain of methylation at Q163 (P = 0.0074)
MVP		0.60
MPC		0.81
ClinPred		0.38	T
GERP RS		4.6
Varity_R		0.21
gMVP		0.30
Mutation Taster		=87/13	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

hg19: chr7-40172711;