7-40132906-T-G

Position:

• chr7-40132906-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138701.4(MPLKIP):​c.*153A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 715,154 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (504 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (185 hom.)
• Consequence: MPLKIP NM_138701.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.142

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-40132906-T-G is Benign according to our data. Variant chr7-40132906-T-G is described in ClinVar as [Benign]. Clinvar id is 1235543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPLKIP	NM_138701.4	c.*153A>C		3_prime_UTR_variant	2/2	ENST00000306984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPLKIP	ENST00000306984.8	c.*153A>C		3_prime_UTR_variant	2/2	1	NM_138701.4	P1

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6728 AN: 152124 Hom.: 499 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0353

GnomAD4 exome AF: 0.00537 AC: 3021 AN: 562912 Hom.: 185 Cov.: 7 AF XY: 0.00447 AC XY: 1339 AN XY: 299480

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000423

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000475

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0444 AC: 6759 AN: 152242 Hom.: 504 Cov.: 33 AF XY: 0.0429 AC XY: 3196 AN XY: 74448

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.00428 Hom.: 61

Bravo AF: 0.0504

Asia WGS AF: 0.0140 AC: 49 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12146; hg19: chr7-40172505;