rs6502557

Positions:

• chr17-17057664-G-A
• chr17-17057664-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364716.4(MPRIP):​c.123+14693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 717,724 control chromosomes in the GnomAD database, including 8,947 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2055 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6892 hom.)
• Consequence: MPRIP NM_001364716.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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 (MetaRNN=0.0033490062).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPRIP	NM_001364716.4	c.123+14693G>A		intron_variant		ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2	c.123+14693G>A		intron_variant			NM_001364716.4	ENSP00000498253	A2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24402 AN: 151848 Hom.: 2052 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.146 AC: 22136 AN: 151582 Hom.: 1788 AF XY: 0.147 AC XY: 11894 AN XY: 81096

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.151 AC: 85622 AN: 565758 Hom.: 6892 Cov.: 0 AF XY: 0.151 AC XY: 45964 AN XY: 305214

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.161 AC: 24413 AN: 151966 Hom.: 2055 Cov.: 32 AF XY: 0.161 AC XY: 11939 AN XY: 74270

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.189

Alfa AF: 0.163 Hom.: 2763

Bravo AF: 0.168

TwinsUK AF: 0.157 AC: 583

ALSPAC AF: 0.144 AC: 554

ExAC AF: 0.134 AC: 2906

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.045
DANN	Benign	0.51
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00022	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.014
Sift	Pathogenic	0.0	D
Vest4		0.015
ClinPred		0.0044	T
GERP RS		-1.5

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: rs6502557; hg19: chr17-16960978; COSMIC: COSV59044965;