Variant 7-40132833-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138701.4(MPLKIP):c.*226G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 549,930 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

MPLKIP
NM_138701.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0730

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 7-40132833-C-T is Benign according to our data. Variant chr7-40132833-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00906 (1378/152148) while in subpopulation AFR AF= 0.0306 (1271/41500). AF 95% confidence interval is 0.0292. There are 18 homozygotes in gnomad4. There are 633 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPLKIP	NM_138701.4 linkuse as main transcript	c.*226G>A		3_prime_UTR_variant	2/2	ENST00000306984.8	NP_619646.1	Q8TAP9A4D1W6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPLKIP	ENST00000306984 linkuse as main transcript	c.*226G>A		3_prime_UTR_variant	2/2	1	NM_138701.4	ENSP00000304553.5		Q8TAP9

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1370

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00813

GnomAD4 exome

AF:

0.00132

AC:

527

AN:

397782

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

231

AN XY:

211916

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000381

Gnomad4 SAS exome

AF:

0.0000922

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.00304

GnomAD4 genome

AF:

0.00906

AC:

1378

AN:

152148

Hom.:

Cov.:

AF XY:

0.00851

AC XY:

633

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0306

Gnomad4 AMR

AF:

0.00465

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00794

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.00491

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over