17-17136299-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_001364716.4(MPRIP):c.585A>G(p.Lys195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,800 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (13 hom.)
• Consequence: MPRIP NM_001364716.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280

Genes affected

MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-17136299-A-G is Benign according to our data. Variant chr17-17136299-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.028 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00196 (2869/1461648) while in subpopulation MID AF= 0.0248 (143/5768). AF 95% confidence interval is 0.0215. There are 13 homozygotes in gnomad4_exome. There are 1570 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPRIP	NM_001364716.4	c.585A>G	p.Lys195=	synonymous_variant	6/24	ENST00000651222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPRIP	ENST00000651222.2	c.585A>G	p.Lys195=	synonymous_variant	6/24		NM_001364716.4	A2

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 330 AN: 152034 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00260 AC: 648 AN: 249614 Hom.: 1 AF XY: 0.00310 AC XY: 419 AN XY: 135064

Gnomad AFR exome AF: 0.000434

Gnomad AMR exome AF: 0.00192

Gnomad ASJ exome AF: 0.00200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00468

Gnomad FIN exome AF: 0.00144

Gnomad NFE exome AF: 0.00296

Gnomad OTH exome AF: 0.00789

GnomAD4 exome AF: 0.00196 AC: 2869 AN: 1461648 Hom.: 13 Cov.: 35 AF XY: 0.00216 AC XY: 1570 AN XY: 727116

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00210

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00471

Gnomad4 FIN exome AF: 0.00122

Gnomad4 NFE exome AF: 0.00169

Gnomad4 OTH exome AF: 0.00305

GnomAD4 genome AF: 0.00218 AC: 331 AN: 152152 Hom.: 1 Cov.: 33 AF XY: 0.00242 AC XY: 180 AN XY: 74378

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00478

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00272

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00288 Hom.: 0

Bravo AF: 0.00251

EpiCase AF: 0.00431

EpiControl AF: 0.00434

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

MPRIP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.0
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs147247641; hg19: chr17-17039613; COSMIC: COSV100506272; COSMIC: COSV100506272;