rs10756457

Variant names:

• chr9-13150532-T-C
• rs10756457
• NM_001378778.1:c.3609A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-13150532-T-C
• chr9-13150532-T-A
• chr9-13150532-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378778.1(MPDZ):​c.3609A>G​(p.Lys1203Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,568,516 control chromosomes in the GnomAD database, including 95,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14582 hom., cov: 31)
  • Exomes 𝑓: 0.33 (80612 hom.)
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.31
• Publications: 21 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 9-13150532-T-C is Benign according to our data. Variant chr9-13150532-T-C is described in ClinVar as Benign. ClinVar VariationId is 158891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

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.3609A>G	p.Lys1203Lys	synonymous	Exon 25 of 47	NP_001365707.1	O75970-1
	MPDZ	NM_001375413.1		c.3609A>G	p.Lys1203Lys	synonymous	Exon 25 of 48	NP_001362342.1
	MPDZ	NM_001330637.2		c.3609A>G	p.Lys1203Lys	synonymous	Exon 25 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.3609A>G	p.Lys1203Lys	synonymous	Exon 25 of 47	ENSP00000320006.7	O75970-1
	MPDZ	ENST00000541718.5	TSL:1	c.3609A>G	p.Lys1203Lys	synonymous	Exon 25 of 46	ENSP00000439807.1	O75970-2
	MPDZ	ENST00000447879.6	TSL:1	c.3609A>G	p.Lys1203Lys	synonymous	Exon 25 of 46	ENSP00000415208.1	O75970-3

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63190 AN: 151476 Hom.: 14559 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.403

GnomAD2 exomes AF: 0.345 AC: 79984 AN: 232134 AF XY: 0.343

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.459

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.331 AC: 468960 AN: 1416922 Hom.: 80612 Cov.: 33 AF XY: 0.331 AC XY: 233149 AN XY: 703842

African (AFR) AF: 0.625 AC: 19716 AN: 31536

American (AMR) AF: 0.325 AC: 13625 AN: 41974

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 7897 AN: 25170

East Asian (EAS) AF: 0.490 AC: 18301 AN: 37348

South Asian (SAS) AF: 0.380 AC: 29563 AN: 77794

European-Finnish (FIN) AF: 0.280 AC: 14452 AN: 51622

Middle Eastern (MID) AF: 0.354 AC: 1982 AN: 5592

European-Non Finnish (NFE) AF: 0.315 AC: 343024 AN: 1087730

Other (OTH) AF: 0.351 AC: 20400 AN: 58156

GnomAD4 genome AF: 0.417 AC: 63261 AN: 151594 Hom.: 14582 Cov.: 31 AF XY: 0.417 AC XY: 30864 AN XY: 74058

African (AFR) AF: 0.620 AC: 25631 AN: 41346

American (AMR) AF: 0.402 AC: 6109 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3458

East Asian (EAS) AF: 0.481 AC: 2455 AN: 5102

South Asian (SAS) AF: 0.395 AC: 1895 AN: 4802

European-Finnish (FIN) AF: 0.297 AC: 3128 AN: 10534

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21656 AN: 67872

Other (OTH) AF: 0.405 AC: 849 AN: 2094

Alfa AF: 0.350 Hom.: 17063

Bravo AF: 0.431

Asia WGS AF: 0.460 AC: 1597 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.8
DANN	Benign	0.45
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10756457; hg19: chr9-13150531; COSMIC: COSV59916228;