chr9-13107076-G-A

Variant names:

• chr9-13107076-G-A
• rs200049739
• NM_001378778.1:c.6102C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_001378778.1(MPDZ):​c.6102C>T​(p.Gly2034Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,585,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.47
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hydrocephalus, nonsyndromic, autosomal recessive 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-13107076-G-A is Benign according to our data. Variant chr9-13107076-G-A is described in ClinVar as Benign. ClinVar VariationId is 738424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000591 (90/152216) while in subpopulation AFR AF = 0.00188 (78/41534). AF 95% confidence interval is 0.00154. There are 0 homozygotes in GnomAd4. There are 40 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378778.1. 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
	MPDZ	NM_001378778.1	MANE Select	c.6102C>T	p.Gly2034Gly	synonymous	Exon 47 of 47	NP_001365707.1	O75970-1
	MPDZ	NM_001375413.1		c.6201C>T	p.Gly2067Gly	synonymous	Exon 48 of 48	NP_001362342.1
	MPDZ	NM_001330637.2		c.6102C>T	p.Gly2034Gly	synonymous	Exon 47 of 47	NP_001317566.1	O75970-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.6102C>T	p.Gly2034Gly	synonymous	Exon 47 of 47	ENSP00000320006.7	O75970-1
	MPDZ	ENST00000541718.5	TSL:1	c.6015C>T	p.Gly2005Gly	synonymous	Exon 46 of 46	ENSP00000439807.1	O75970-2
	MPDZ	ENST00000447879.6	TSL:1	c.6003C>T	p.Gly2001Gly	synonymous	Exon 46 of 46	ENSP00000415208.1	O75970-3

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000157 AC: 39 AN: 247992 AF XY: 0.000119

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000170 AC: 244 AN: 1433632 Hom.: 0 Cov.: 30 AF XY: 0.000182 AC XY: 129 AN XY: 709892

African (AFR) AF: 0.00166 AC: 55 AN: 33166

American (AMR) AF: 0.0000676 AC: 3 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25554

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39178

South Asian (SAS) AF: 0.00 AC: 0 AN: 83480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52604

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5652

European-Non Finnish (NFE) AF: 0.000156 AC: 170 AN: 1090756

Other (OTH) AF: 0.000204 AC: 12 AN: 58886

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40 AN XY: 74436

African (AFR) AF: 0.00188 AC: 78 AN: 41534

American (AMR) AF: 0.000719 AC: 11 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.000691

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MPDZ-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		-1.5

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

Other links and lift over

dbSNP: rs200049739; hg19: chr9-13107075; COSMIC: COSV59917561;