Genetic Variant NM_015460.4:c.682C>A (chr3-40167192-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015460.4(MYRIP):c.682C>A(p.His228Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000326 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

MYRIP
NM_015460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Publications

4 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08053282).

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.682C>A	p.His228Asn	missense	Exon 7 of 17	NP_056275.2	Q8NFW9-1
MYRIP	NM_001284423.2		c.682C>A	p.His228Asn	missense	Exon 7 of 17	NP_001271352.1	Q8NFW9-1
MYRIP	NM_001284424.2		c.682C>A	p.His228Asn	missense	Exon 7 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.682C>A	p.His228Asn	missense	Exon 7 of 17	ENSP00000301972.6	Q8NFW9-1
MYRIP	ENST00000444716.5	TSL:1	c.682C>A	p.His228Asn	missense	Exon 7 of 17	ENSP00000398665.1	Q8NFW9-1
MYRIP	ENST00000396217.7	TSL:1	c.415C>A	p.His139Asn	missense	Exon 6 of 16	ENSP00000379519.3	Q8NFW9-6

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000283

AC:

AN:

251070

AF XY:

0.000243

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000314

AC:

459

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000872

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000362

AC:

403

AN:

1112004

Other (OTH)

AF:

0.000232

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000440

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41442

American (AMR)

AF:

0.00190

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000319

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

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

0.28

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.017

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

PhyloP100

4.4

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.13

Sift

Benign

0.062

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.49

MVP

0.56

MPC

0.55

ClinPred

0.23

GERP RS

4.3

Varity_R

0.32

gMVP

0.51

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

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