Variant 3-40044269-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000396217.7(MYRIP):c.200G>A(p.Arg67Gln) variant causes a missense, splice region 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. 14/17 in silico tools predict 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
ENST00000396217.7 missense, splice_region

Scores

Splicing: ADA: 0.000001669

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0220

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 made for transcript

Verdict is Benign. Variant got -10 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. Variant chr3-40044269-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRIP	NM_015460.4 linkuse as main transcript	c.330G>A	p.Ala110=	splice_region_variant, synonymous_variant	3/17	ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11 linkuse as main transcript	c.330G>A	p.Ala110=	splice_region_variant, synonymous_variant	3/17	1	NM_015460.4	ENSP00000301972	P1	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

GnomAD3 exomes

AF:

0.00216

AC:

539

AN:

249996

Hom.:

AF XY:

0.00243

AC XY:

329

AN XY:

135202

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 SAS exome

AF:

0.00199

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

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00244

Gnomad4 ASJ exome

AF:

0.00402

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00217

Gnomad4 FIN exome

AF:

0.000730

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00169

AC:

257

AN:

152328

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00262

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00226

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2018

- -

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

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

MutationTaster

Benign

1.0

D;D;D;N

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over