Genetic Variant NM_001364716.4:c.103A>C (chr17-17042951-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001364716.4(MPRIP):c.103A>C(p.Asn35His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N35D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MPRIP
NM_001364716.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.42

Publications

0 publications found

Variant links:

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]

MPRIP links:

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ACMG classification

Classification was made for transcript

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=0.19325197).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPRIP	NM_001364716.4	MANE Select	c.103A>C	p.Asn35His	missense	Exon 1 of 24	NP_001351645.2	A0A494BZV2
MPRIP	NM_015134.4		c.103A>C	p.Asn35His	missense	Exon 1 of 23	NP_055949.2	Q6WCQ1-2
MPRIP	NM_201274.4		c.103A>C	p.Asn35His	missense	Exon 1 of 24	NP_958431.2	Q6WCQ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPRIP	ENST00000651222.2	MANE Select	c.103A>C	p.Asn35His	missense	Exon 1 of 24	ENSP00000498253.1	A0A494BZV2
MPRIP	ENST00000395811.9	TSL:1	c.103A>C	p.Asn35His	missense	Exon 1 of 23	ENSP00000379156.4	Q6WCQ1-2
MPRIP	ENST00000948254.1		c.103A>C	p.Asn35His	missense	Exon 1 of 22	ENSP00000618313.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458764

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725708

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5282

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110794

Other (OTH)

AF:

0.00

AC:

AN:

60222

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.033

Eigen

Benign

0.11

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

3.4

PROVEAN

Benign

-2.1

REVEL

Benign

0.11

Sift

Uncertain

0.0090

Sift4G

Benign

0.086

Polyphen

0.96

Vest4

0.28

MutPred

0.22

Loss of loop (P = 0.0112)

MVP

0.17

MPC

1.9

ClinPred

0.64

GERP RS

3.4

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.59

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over