Genetic Variant MYO16:p.Pro853Ala (chr13-109009011-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001198950.3(MYO16):c.2557C>G(p.Pro853Ala) variant causes a missense change. The variant allele was found at a frequency of 0.393 in 1,598,464 control chromosomes in the GnomAD database, including 126,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 11736 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115233 hom. )

Consequence

MYO16
NM_001198950.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.92

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.509407E-5).

BP6

Variant 13-109009011-C-G is Benign according to our data. Variant chr13-109009011-C-G is described in ClinVar as [Benign]. Clinvar id is 3059068.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO16	NM_001198950.3 link	c.2557C>G	p.Pro853Ala	missense_variant	Exon 22 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.2557C>G	p.Pro853Ala	missense_variant	Exon 22 of 35	1	NM_001198950.3	ENSP00000401633.3	F8W883
MYO16	ENST00000356711.7 link	c.2491C>G	p.Pro831Ala	missense_variant	Exon 22 of 35	1		ENSP00000349145.2	Q9Y6X6-1
MYO16	ENST00000251041.10 link	c.2491C>G	p.Pro831Ala	missense_variant	Exon 22 of 25	5		ENSP00000251041.5	Q9Y6X6-3
MYO16	ENST00000375857.6 link	n.1877C>G		non_coding_transcript_exon_variant	Exon 17 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58816

AN:

151904

Hom.:

11730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.435

AC:

105227

AN:

242026

Hom.:

23909

AF XY:

0.435

AC XY:

56983

AN XY:

131010

show subpopulations

Gnomad AFR exome

AF:

0.337

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.668

Gnomad SAS exome

AF:

0.513

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.393

AC:

568933

AN:

1446442

Hom.:

115233

Cov.:

AF XY:

0.396

AC XY:

285037

AN XY:

719058

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.387

AC:

58840

AN:

152022

Hom.:

11736

Cov.:

AF XY:

0.396

AC XY:

29432

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.659

Gnomad4 SAS

AF:

0.511

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.368

Hom.:

7878

Bravo

AF:

0.380

TwinsUK

AF:

0.371

AC:

1377

ALSPAC

AF:

0.381

AC:

1467

ESP6500AA

AF:

0.340

AC:

1496

ESP6500EA

AF:

0.376

AC:

3231

ExAC

AF:

0.431

AC:

52323

Asia WGS

AF:

0.558

AC:

1941

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 17, 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

0.081

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.17

T;T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.000095

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

L;.;L;L

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.2

D;.;D;D

REVEL

Uncertain

0.44

Sift

Benign

0.20

T;.;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.97

D;.;.;D

Vest4

0.088

MPC

0.54

ClinPred

0.029

GERP RS

5.7

Varity_R

0.22

gMVP

0.32

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