chr17-17042904-A-G

Variant names:

• chr17-17042904-A-G
• rs145264583
• NM_001364716.4:c.56A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364716.4(MPRIP):​c.56A>G​(p.Lys19Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,610,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21024054).

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.56A>G	p.Lys19Arg	missense	Exon 1 of 24	NP_001351645.2	A0A494BZV2
	MPRIP	NM_015134.4		c.56A>G	p.Lys19Arg	missense	Exon 1 of 23	NP_055949.2	Q6WCQ1-2
	MPRIP	NM_201274.4		c.56A>G	p.Lys19Arg	missense	Exon 1 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.56A>G	p.Lys19Arg	missense	Exon 1 of 24	ENSP00000498253.1	A0A494BZV2
	MPRIP	ENST00000395811.9	TSL:1	c.56A>G	p.Lys19Arg	missense	Exon 1 of 23	ENSP00000379156.4	Q6WCQ1-2
	MPRIP	ENST00000948254.1		c.56A>G	p.Lys19Arg	missense	Exon 1 of 22	ENSP00000618313.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152030 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248420 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000897

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000960 AC: 14 AN: 1458120 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8 AN XY: 725402

African (AFR) AF: 0.000210 AC: 7 AN: 33352

American (AMR) AF: 0.0000448 AC: 2 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4464

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110976

Other (OTH) AF: 0.00 AC: 0 AN: 60166

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152030 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74250

African (AFR) AF: 0.0000966 AC: 4 AN: 41420

American (AMR) AF: 0.000131 AC: 2 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Benign	0.92
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.3
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MVP		0.39
MPC		2.1
ClinPred		0.49	T
GERP RS		1.8
PromoterAI		-0.083	Neutral
Varity_R		0.19
gMVP		0.94
Mutation Taster		=66/34	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: rs145264583; hg19: chr17-16946218;