dbSNP rs763591576: MYRIP:p.Gly184Glu (chr3-40166846-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015460.4(MYRIP):c.551G>A(p.Gly184Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000874 in 1,601,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

MYRIP
NM_015460.4 missense, splice_region

Scores

Splicing: ADA: 0.9990

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15

Publications

0 publications found

Variant links:

Genes affected

MYRIP (HGNC:19156): (myosin VIIA and Rab interacting protein) Predicted to enable actin binding activity and myosin binding activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be located in actin cytoskeleton; dense core granule; and perinuclear region of cytoplasm. Predicted to be part of exocyst. Predicted to be active in cortical actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MYRIP links:

ENTPD3-AS1 (HGNC:):

ENTPD3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYRIP	NM_015460.4	MANE Select	c.551G>A	p.Gly184Glu	missense splice_region	Exon 6 of 17	NP_056275.2	Q8NFW9-1
MYRIP	NM_001284423.2		c.551G>A	p.Gly184Glu	missense splice_region	Exon 6 of 17	NP_001271352.1	Q8NFW9-1
MYRIP	NM_001284424.2		c.551G>A	p.Gly184Glu	missense splice_region	Exon 6 of 16	NP_001271353.1	Q8NFW9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYRIP	ENST00000302541.11	TSL:1 MANE Select	c.551G>A	p.Gly184Glu	missense splice_region	Exon 6 of 17	ENSP00000301972.6	Q8NFW9-1
MYRIP	ENST00000444716.5	TSL:1	c.551G>A	p.Gly184Glu	missense splice_region	Exon 6 of 17	ENSP00000398665.1	Q8NFW9-1
MYRIP	ENST00000396217.7	TSL:1	c.284G>A	p.Gly95Glu	missense splice_region	Exon 5 of 16	ENSP00000379519.3	Q8NFW9-6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

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:

0.0000478

AC:

AN:

251088

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000828

AC:

AN:

1449550

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

722020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33224

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.000303

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

86002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100864

Other (OTH)

AF:

0.00

AC:

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.4

PhyloP100

8.1

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.23

Sift

Benign

0.10

Sift4G

Benign

0.52

Polyphen

1.0

Vest4

0.80

MutPred

0.36

Gain of solvent accessibility (P = 9e-04)

MVP

0.74

MPC

0.59

ClinPred

0.33

GERP RS

4.5

Varity_R

0.26

gMVP

0.37

Mutation Taster

=36/64

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over