chr17-17164868-G-A

Position:

• chr17-17164868-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001364716.4(MPRIP):​c.3277G>A​(p.Val1093Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,304,052 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0061 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (2 hom.)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00614 (935/152384) while in subpopulation AFR AF= 0.0213 (887/41592). AF 95% confidence interval is 0.0202. There are 15 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPRIP	NM_001364716.4	c.3277G>A	p.Val1093Met	missense_variant	16/24	ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2	c.3277G>A	p.Val1093Met	missense_variant	16/24		NM_001364716.4	ENSP00000498253	A2

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 931 AN: 152266 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00122 AC: 179 AN: 146860 Hom.: 0 AF XY: 0.000935 AC XY: 74 AN XY: 79138

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000445

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.000587 AC: 676 AN: 1151668 Hom.: 2 Cov.: 29 AF XY: 0.000510 AC XY: 288 AN XY: 564688

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.000920

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000171

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000239

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00614 AC: 935 AN: 152384 Hom.: 15 Cov.: 33 AF XY: 0.00619 AC XY: 461 AN XY: 74520

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00264 Hom.: 2

Bravo AF: 0.00684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.7
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs61744862; hg19: chr17-17068182;