17-17136299-A-G

Variant names:

• chr17-17136299-A-G
• rs147247641
• NM_001364716.4:c.585A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001364716.4(MPRIP):​c.585A>G​(p.Lys195Lys) 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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -15 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. GnomAdExome4 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 GnomAdExome4. There are 1570 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4	c.585A>G	p.Lys195Lys	synonymous_variant	Exon 6 of 24	ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2	c.585A>G	p.Lys195Lys	synonymous_variant	Exon 6 of 24		NM_001364716.4	ENSP00000498253.1

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

GnomAD2 exomes AF: 0.00260 AC: 648 AN: 249614 AF XY: 0.00310

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 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

African (AFR) AF: 0.00111 AC: 37 AN: 33472

American (AMR) AF: 0.00210 AC: 94 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00214 AC: 56 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00471 AC: 406 AN: 86248

European-Finnish (FIN) AF: 0.00122 AC: 65 AN: 53368

Middle Eastern (MID) AF: 0.0248 AC: 143 AN: 5768

European-Non Finnish (NFE) AF: 0.00169 AC: 1884 AN: 1111878

Other (OTH) AF: 0.00305 AC: 184 AN: 60384

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

African (AFR) AF: 0.000482 AC: 20 AN: 41494

American (AMR) AF: 0.00379 AC: 58 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00478 AC: 23 AN: 4816

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10590

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00272 AC: 185 AN: 67998

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

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

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.028
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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