rs755592837

Variant names:

• chr17-17136424-G-A
• rs755592837
• NM_001364716.4:c.710G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001364716.4(MPRIP):​c.710G>A​(p.Arg237Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,610,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055233747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364716.4. 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
	MPRIP	NM_001364716.4	MANE Select	c.710G>A	p.Arg237Gln	missense	Exon 6 of 24	NP_001351645.2	A0A494BZV2
	MPRIP	NM_015134.4		c.710G>A	p.Arg237Gln	missense	Exon 6 of 23	NP_055949.2	Q6WCQ1-2
	MPRIP	NM_201274.4		c.710G>A	p.Arg237Gln	missense	Exon 6 of 24	NP_958431.2	Q6WCQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPRIP	ENST00000651222.2	MANE Select	c.710G>A	p.Arg237Gln	missense	Exon 6 of 24	ENSP00000498253.1	A0A494BZV2
	MPRIP	ENST00000395811.9	TSL:1	c.710G>A	p.Arg237Gln	missense	Exon 6 of 23	ENSP00000379156.4	Q6WCQ1-2
	MPRIP	ENST00000584067.5	TSL:1	c.242G>A	p.Arg81Gln	missense	Exon 2 of 18	ENSP00000462688.1	J3KSW8

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000496 AC: 12 AN: 241920 AF XY: 0.0000458

Gnomad AFR exome AF: 0.0000658

Gnomad AMR exome AF: 0.0000886

Gnomad ASJ exome AF: 0.000407

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000276

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000439 AC: 64 AN: 1457834 Hom.: 0 Cov.: 35 AF XY: 0.0000566 AC XY: 41 AN XY: 724832

African (AFR) AF: 0.000150 AC: 5 AN: 33350

American (AMR) AF: 0.0000678 AC: 3 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.000846 AC: 22 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00 AC: 0 AN: 85452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53048

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1110238

Other (OTH) AF: 0.000166 AC: 10 AN: 60230

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.000262 AC: 4 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.1
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.026
Sift	Benign	0.30	T
Sift4G	Benign	0.46	T
Polyphen		0.61	P
Vest4		0.20
MutPred		0.15		Gain of loop (P = 0.024)
MVP		0.34
MPC		0.39
ClinPred		0.027	T
GERP RS		3.4
PromoterAI		-0.0053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.18
Mutation Taster		=95/5	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: rs755592837; hg19: chr17-17039738; COSMIC: COSV105198368;