Genetic Variant MYRIP:p.Arg67Gln (chr3-40044269-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015460.4(MYRIP):c.330G>A(p.Ala110Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,613,990 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

MYRIP
NM_015460.4 splice_region, synonymous

Scores

Splicing: ADA: 0.000001669

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0220

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00632897).

BP6

Variant 3-40044269-G-A is Benign according to our data. Variant chr3-40044269-G-A is described in ClinVar as [Benign]. Clinvar id is 771852.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.022 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRIP	NM_015460.4 link	c.330G>A	p.Ala110Ala	splice_region_variant, synonymous_variant	Exon 3 of 17	ENST00000302541.11	NP_056275.2	Q8NFW9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11 link	c.330G>A	p.Ala110Ala	splice_region_variant, synonymous_variant	Exon 3 of 17	1	NM_015460.4	ENSP00000301972.6		Q8NFW9-1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00216

AC:

539

AN:

249996

AF XY:

0.00243

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00389

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00246

AC:

3593

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1806

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33476

American (AMR)

AF:

0.00244

AC:

109

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00402

AC:

105

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00217

AC:

187

AN:

86242

European-Finnish (FIN)

AF:

0.000730

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00263

AC:

2926

AN:

1111838

Other (OTH)

AF:

0.00242

AC:

146

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

178

356

533

711

889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00169

AC:

257

AN:

152328

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000529

AC:

AN:

41582

American (AMR)

AF:

0.00170

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00124

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00262

AC:

178

AN:

68032

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00171

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00216

AC:

262

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00439

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.4

(source)

DANN

Benign

0.90

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.40

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.0

PhyloP100

0.022

PROVEAN

Benign

-0.22

REVEL

Benign

0.034

Sift

Uncertain

0.0080

Sift4G

Benign

0.38

Vest4

0.22

MVP

0.15

ClinPred

0.011

GERP RS

-11

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000017

dbscSNV1_RF

Benign

0.058

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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3-40044269-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over