chr17-17136247-CCAGCAGCAGCAGCAGCAG-C

Variant names:

• chr17-17136247-CCAGCAGCAGCAGCAGCAG-C
• rs3833098
• NM_001364716.4:c.551_568delGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001364716.4(MPRIP):​c.551_568delGCAGCAGCAGCAGCAGCA​(p.Ser184_Ser189del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000662 in 1,555,910 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: MPRIP NM_001364716.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 15 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 -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001364716.4

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.551_568delGCAGCAGCAGCAGCAGCA	p.Ser184_Ser189del	disruptive_inframe_deletion	Exon 6 of 24	NP_001351645.2	A0A494BZV2
	MPRIP	NM_015134.4		c.551_568delGCAGCAGCAGCAGCAGCA	p.Ser184_Ser189del	disruptive_inframe_deletion	Exon 6 of 23	NP_055949.2	Q6WCQ1-2
	MPRIP	NM_201274.4		c.551_568delGCAGCAGCAGCAGCAGCA	p.Ser184_Ser189del	disruptive_inframe_deletion	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.551_568delGCAGCAGCAGCAGCAGCA	p.Ser184_Ser189del	disruptive_inframe_deletion	Exon 6 of 24	ENSP00000498253.1	A0A494BZV2
	MPRIP	ENST00000395811.9	TSL:1	c.551_568delGCAGCAGCAGCAGCAGCA	p.Ser184_Ser189del	disruptive_inframe_deletion	Exon 6 of 23	ENSP00000379156.4	Q6WCQ1-2
	MPRIP	ENST00000584067.5	TSL:1	c.83_100delGCAGCAGCAGCAGCAGCA	p.Ser28_Ser33del	disruptive_inframe_deletion	Exon 2 of 18	ENSP00000462688.1	J3KSW8

Frequencies

GnomAD3 genomes AF: 0.000525 AC: 79 AN: 150558 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000423

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000872

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.000666 AC: 143 AN: 214846 AF XY: 0.000659

Gnomad AFR exome AF: 0.000451

Gnomad AMR exome AF: 0.000100

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000642

Gnomad FIN exome AF: 0.0000518

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.000383

GnomAD4 exome AF: 0.000677 AC: 951 AN: 1405238 Hom.: 1 AF XY: 0.000644 AC XY: 450 AN XY: 699134

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000403 AC: 13 AN: 32274

American (AMR) AF: 0.0000941 AC: 4 AN: 42486

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25202

East Asian (EAS) AF: 0.000160 AC: 6 AN: 37396

South Asian (SAS) AF: 0.000205 AC: 17 AN: 82924

European-Finnish (FIN) AF: 0.000141 AC: 7 AN: 49608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.000829 AC: 888 AN: 1071808

Other (OTH) AF: 0.000259 AC: 15 AN: 57900

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000524 AC: 79 AN: 150672 Hom.: 0 Cov.: 0 AF XY: 0.000476 AC XY: 35 AN XY: 73550

African (AFR) AF: 0.000366 AC: 15 AN: 40966

American (AMR) AF: 0.000132 AC: 2 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.000423 AC: 2 AN: 4728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000872 AC: 59 AN: 67626

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000694 Hom.: 3215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=186/14	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3833098; hg19: chr17-17039561;