rs61744862

Variant names:

• chr17-17164868-G-A
• rs61744862
• NM_001364716.4:c.3277G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-17164868-G-A
• chr17-17164868-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001364716.4(MPRIP):​c.3277G>A​(p.Val1093Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,304,052 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0061 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (2 hom.)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 10 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.063).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00614 (935/152384) while in subpopulation AFR AF = 0.0213 (887/41592). AF 95% confidence interval is 0.0202. There are 15 homozygotes in GnomAd4. There are 461 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 gene

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.3277G>A	p.Val1093Met	missense	Exon 16 of 24	NP_001351645.2	A0A494BZV2
	MPRIP	NM_015134.4		c.2163+3512G>A		intron	N/A	NP_055949.2	Q6WCQ1-2
	MPRIP	NM_201274.4		c.2163+3512G>A		intron	N/A	NP_958431.2	Q6WCQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPRIP	ENST00000651222.2	MANE Select	c.3277G>A	p.Val1093Met	missense	Exon 16 of 24	ENSP00000498253.1	A0A494BZV2
	MPRIP	ENST00000395811.9	TSL:1	c.2163+3512G>A		intron	N/A	ENSP00000379156.4	Q6WCQ1-2
	MPRIP	ENST00000584067.5	TSL:1	c.1581+3512G>A		intron	N/A	ENSP00000462688.1	J3KSW8

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 931 AN: 152266 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00122 AC: 179 AN: 146860 AF XY: 0.000935

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.000587 AC: 676 AN: 1151668 Hom.: 2 Cov.: 29 AF XY: 0.000510 AC XY: 288 AN XY: 564688

African (AFR) AF: 0.0228 AC: 556 AN: 24412

American (AMR) AF: 0.000920 AC: 26 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15934

East Asian (EAS) AF: 0.00 AC: 0 AN: 12844

South Asian (SAS) AF: 0.000171 AC: 13 AN: 76160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27178

Middle Eastern (MID) AF: 0.000909 AC: 4 AN: 4402

European-Non Finnish (NFE) AF: 0.0000239 AC: 22 AN: 920866

Other (OTH) AF: 0.00132 AC: 55 AN: 41614

GnomAD4 genome AF: 0.00614 AC: 935 AN: 152384 Hom.: 15 Cov.: 33 AF XY: 0.00619 AC XY: 461 AN XY: 74520

African (AFR) AF: 0.0213 AC: 887 AN: 41592

American (AMR) AF: 0.00229 AC: 35 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68042

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00385 Hom.: 30

Bravo AF: 0.00684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	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: rs61744862; hg19: chr17-17068182;