17-17075720-T-C

Variant names:

• chr17-17075720-T-C
• NM_001364716.4:c.134T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001364716.4(MPRIP):​c.134T>C​(p.Ile45Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4	c.134T>C	p.Ile45Thr	missense_variant	Exon 2 of 24	ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2	c.134T>C	p.Ile45Thr	missense_variant	Exon 2 of 24		NM_001364716.4	ENSP00000498253.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.134T>C (p.I45T) alteration is located in exon 2 (coding exon 2) of the MPRIP gene. This alteration results from a T to C substitution at nucleotide position 134, causing the isoleucine (I) at amino acid position 45 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.1	.;M;M
PROVEAN	Benign	-0.98	.;N;N
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.99, 0.64	.;D;P
Vest4		0.65, 0.78
MutPred		0.63		Loss of catalytic residue at I45 (P = 0.0022);Loss of catalytic residue at I45 (P = 0.0022);Loss of catalytic residue at I45 (P = 0.0022);
MVP		0.90
MPC		2.5
ClinPred		0.85	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-16979034;