17-17042951-A-G

Variant names:

• chr17-17042951-A-G
• rs1226623799
• NM_001364716.4:c.103A>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.103A>G​(p.Asn35Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42
• 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=0.12599319).

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.103A>G	p.Asn35Asp	missense	Exon 1 of 24	NP_001351645.2	A0A494BZV2
	MPRIP	NM_015134.4		c.103A>G	p.Asn35Asp	missense	Exon 1 of 23	NP_055949.2	Q6WCQ1-2
	MPRIP	NM_201274.4		c.103A>G	p.Asn35Asp	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.103A>G	p.Asn35Asp	missense	Exon 1 of 24	ENSP00000498253.1	A0A494BZV2
	MPRIP	ENST00000395811.9	TSL:1	c.103A>G	p.Asn35Asp	missense	Exon 1 of 23	ENSP00000379156.4	Q6WCQ1-2
	MPRIP	ENST00000948254.1		c.103A>G	p.Asn35Asp	missense	Exon 1 of 22	ENSP00000618313.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000403 AC: 1 AN: 248112 AF XY: 0.00000741

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000206 AC: 3 AN: 1458764 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 725708

African (AFR) AF: 0.0000599 AC: 2 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110794

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74274

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	0.38
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.4
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.068
Sift	Benign	0.038	D
Sift4G	Benign	0.38	T
Polyphen		0.34	B
Vest4		0.17
MutPred		0.22		Loss of loop (P = 0.0288)
MVP		0.13
MPC		1.3
ClinPred		0.47	T
GERP RS		3.4
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.60
Mutation Taster		=85/15	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: rs1226623799; hg19: chr17-16946265;