Variant 9-13126598-G-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_001378778.1(MPDZ):c.4558-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 1,607,520 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 7 hom. )

Consequence

MPDZ
NM_001378778.1 splice_region, intron

Scores

Splicing: ADA: 0.05545

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

MPDZ (HGNC:7208): (multiple PDZ domain crumbs cell polarity complex component) The protein encoded by this gene has multiple PDZ domains, which are hallmarks of protein-protein interactions. The encoded protein is known to interact with the HTR2C receptor and may cause it to clump at the cell surface. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

MPDZ links:

MPDZ (HGNC:):

MPDZ links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 9-13126598-G-T is Benign according to our data. Variant chr9-13126598-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 211515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-13126598-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00492 (749/152280) while in subpopulation AFR AF= 0.0171 (710/41570). AF 95% confidence interval is 0.016. There are 4 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1 linkuse as main transcript	c.4558-8C>A		splice_region_variant, intron_variant		ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12 linkuse as main transcript	c.4558-8C>A		splice_region_variant, intron_variant		5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

747

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00127

AC:

302

AN:

237326

Hom.:

AF XY:

0.000981

AC XY:

126

AN XY:

128482

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000468

AC:

681

AN:

1455240

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

292

AN XY:

723222

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00492

AC:

749

AN:

152280

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

351

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00572

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 29, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.1

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.055

dbscSNV1_RF

Benign

0.41

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