chr17-17042853-C-T

Variant names:

• chr17-17042853-C-T
• rs776299638
• NM_001364716.4:c.5C>T

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.5C>T​(p.Ser2Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000134 in 1,561,782 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MPRIP NM_001364716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 1 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=0.25174725).

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.5C>T	p.Ser2Leu	missense	Exon 1 of 24	NP_001351645.2	A0A494BZV2
	MPRIP	NM_015134.4		c.5C>T	p.Ser2Leu	missense	Exon 1 of 23	NP_055949.2	Q6WCQ1-2
	MPRIP	NM_201274.4		c.5C>T	p.Ser2Leu	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.5C>T	p.Ser2Leu	missense	Exon 1 of 24	ENSP00000498253.1	A0A494BZV2
	MPRIP	ENST00000395811.9	TSL:1	c.5C>T	p.Ser2Leu	missense	Exon 1 of 23	ENSP00000379156.4	Q6WCQ1-2
	MPRIP	ENST00000948254.1		c.5C>T	p.Ser2Leu	missense	Exon 1 of 22	ENSP00000618313.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00000508 AC: 1 AN: 196670 AF XY: 0.00000926

Gnomad AFR exome AF: 0.00

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: 0.0000117

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 20 AN: 1410586 Hom.: 0 Cov.: 32 AF XY: 0.0000114 AC XY: 8 AN XY: 700244

African (AFR) AF: 0.0000322 AC: 1 AN: 31054

American (AMR) AF: 0.00 AC: 0 AN: 39318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24858

East Asian (EAS) AF: 0.00 AC: 0 AN: 34906

South Asian (SAS) AF: 0.00 AC: 0 AN: 81812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3990

European-Non Finnish (NFE) AF: 0.0000147 AC: 16 AN: 1087438

Other (OTH) AF: 0.0000520 AC: 3 AN: 57702

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151196 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73810

African (AFR) AF: 0.0000242 AC: 1 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67638

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000837 AC: 1

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	Benign	0.26
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.2
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.055
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.19	B
Vest4		0.22
MutPred		0.23		Gain of stability (P = 0.003)
MVP		0.068
MPC		1.0
ClinPred		0.48	T
GERP RS		2.3
PromoterAI		0.092	Neutral
Varity_R		0.14
gMVP		0.64
Mutation Taster		=74/26	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: rs776299638; hg19: chr17-16946167;