rs911973

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001198950.3(MYO16):c.609T>A(p.Asp203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 1,597,600 control chromosomes in the GnomAD database, including 2,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 250 hom., cov: 33)

Exomes 𝑓: 0.042 ( 2746 hom. )

Consequence

MYO16
NM_001198950.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.13

Publications

13 publications found

Variant links:

Genes affected

MYO16 (HGNC:29822): (myosin XVI) This gene encodes an unconventional myosin protein. The encoded protein has been proposed to act as a serine/threonine phosphatase-1 targeting or regulatory subunit. Studies in a rat cell line suggest that this protein may regulate cell cycle progression. A variant within this gene may be associated with susceptibility to schizophrenia and elevated expression of this gene has been observed in the frontal cortex of human schizophrenia patients. [provided by RefSeq, Mar 2017]

MYO16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015803277).

BP6

Variant 13-108785736-T-A is Benign according to our data. Variant chr13-108785736-T-A is described in ClinVar as Benign. ClinVar VariationId is 3059259.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO16	NM_001198950.3 link	c.609T>A	p.Asp203Glu	missense_variant	Exon 5 of 35	ENST00000457511.7	NP_001185879.1	F8W883

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO16	ENST00000457511.7 link	c.609T>A	p.Asp203Glu	missense_variant	Exon 5 of 35	1	NM_001198950.3	ENSP00000401633.3	F8W883
MYO16	ENST00000356711.7 link	c.543T>A	p.Asp181Glu	missense_variant	Exon 5 of 35	1		ENSP00000349145.2	Q9Y6X6-1
MYO16	ENST00000251041.10 link	c.543T>A	p.Asp181Glu	missense_variant	Exon 5 of 25	5		ENSP00000251041.5	Q9Y6X6-3
MYO16	ENST00000467639.1 link	n.613T>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5082

AN:

152218

Hom.:

249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00779

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.00828

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0528

AC:

12653

AN:

239740

AF XY:

0.0564

show subpopulations

Gnomad AFR exome

AF:

0.00857

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0473

Gnomad EAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.00861

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0419

AC:

60532

AN:

1445264

Hom.:

2746

Cov.:

AF XY:

0.0441

AC XY:

31725

AN XY:

719240

show subpopulations

African (AFR)

AF:

0.00594

AC:

194

AN:

32686

American (AMR)

AF:

0.0324

AC:

1359

AN:

41914

Ashkenazi Jewish (ASJ)

AF:

0.0462

AC:

1182

AN:

25560

East Asian (EAS)

AF:

0.249

AC:

9860

AN:

39578

South Asian (SAS)

AF:

0.124

AC:

10401

AN:

83708

European-Finnish (FIN)

AF:

0.00837

AC:

445

AN:

53144

Middle Eastern (MID)

AF:

0.0338

AC:

192

AN:

5688

European-Non Finnish (NFE)

AF:

0.0306

AC:

33746

AN:

1103270

Other (OTH)

AF:

0.0528

AC:

3153

AN:

59716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2427

4854

7282

9709

12136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1500

3000

4500

6000

7500

<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:

0.0333

AC:

5080

AN:

152336

Hom.:

250

Cov.:

AF XY:

0.0355

AC XY:

2641

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00782

AC:

325

AN:

41576

American (AMR)

AF:

0.0326

AC:

499

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

155

AN:

3470

East Asian (EAS)

AF:

0.238

AC:

1234

AN:

5182

South Asian (SAS)

AF:

0.145

AC:

702

AN:

4826

European-Finnish (FIN)

AF:

0.00828

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0290

AC:

1970

AN:

68028

Other (OTH)

AF:

0.0340

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

236

473

709

946

1182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0370

Hom.:

150

Bravo

AF:

0.0309

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0332

AC:

128

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.0299

AC:

257

ExAC

AF:

0.0524

AC:

6360

Asia WGS

AF:

0.169

AC:

589

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYO16-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.3

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0011

T;T;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.46

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;N

PhyloP100

1.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.63

N;.;N;N

REVEL

Benign

0.046

Sift

Benign

0.58

T;.;T;T

Sift4G

Benign

0.88

T;T;T;T

Polyphen

0.025

B;.;.;B

Vest4

0.085

MutPred

0.12

Gain of disorder (P = 0.2658);.;Gain of disorder (P = 0.2658);Gain of disorder (P = 0.2658);

MPC

0.18

ClinPred

0.0040

GERP RS

2.7

Varity_R

0.041

gMVP

0.12

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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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