Variant 3-40044123-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015460.4(MYRIP):c.184C>A(p.His62Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000247 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

MYRIP
NM_015460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRIP	NM_015460.4 linkuse as main transcript	c.184C>A	p.His62Asn	missense_variant	3/17	ENST00000302541.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRIP	ENST00000302541.11 linkuse as main transcript	c.184C>A	p.His62Asn	missense_variant	3/17	1	NM_015460.4	P1	Q8NFW9-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152224

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

250718

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000263

AC:

385

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000336

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000172

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.184C>A (p.H62N) alteration is located in exon 3 (coding exon 2) of the MYRIP gene. This alteration results from a C to A substitution at nucleotide position 184, causing the histidine (H) at amino acid position 62 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.74

D;D;D;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.068

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.34

B;B;.

Vest4

0.62

MVP

0.69

MPC

0.26

ClinPred

0.17

GERP RS

5.7

Varity_R

0.28

gMVP

0.29

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

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