rs944814693

Variant names:

• chr17-17126706-C-G
• rs944814693
• NM_001364716.4:c.272C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-17126706-C-G
• chr17-17126706-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001364716.4(MPRIP):​c.272C>G​(p.Thr91Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T91M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• Publications: 3 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPRIP	NM_001364716.4	c.272C>G	p.Thr91Arg	missense_variant	Exon 4 of 24	ENST00000651222.2	NP_001351645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPRIP	ENST00000651222.2	c.272C>G	p.Thr91Arg	missense_variant	Exon 4 of 24		NM_001364716.4	ENSP00000498253.1
MPRIP	ENST00000395811.9	c.272C>G	p.Thr91Arg	missense_variant	Exon 4 of 23	1		ENSP00000379156.4
MPRIP	ENST00000341712.8	c.272C>G	p.Thr91Arg	missense_variant	Exon 4 of 24	5		ENSP00000342379.4
MPRIP	ENST00000577514.5	c.272C>G	p.Thr91Arg	missense_variant	Exon 5 of 5	5		ENSP00000462532.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000307 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Uncertain	0.62	D
MutationAssessor	Benign	0.44	.;N;N
PhyloP100		4.1
PROVEAN	Benign	-1.1	.;N;N
REVEL	Uncertain	0.61
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0, 0.98	.;D;D
Vest4		0.60, 0.60
MutPred		0.39		Loss of glycosylation at T91 (P = 0.0103);Loss of glycosylation at T91 (P = 0.0103);Loss of glycosylation at T91 (P = 0.0103);
MVP		0.82
MPC		2.4
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.52		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs944814693; hg19: chr17-17030020;