Variant 13-109179596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001198950.3(MYO16):c.5378C>T(p.Ser1793Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,613,886 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

MYO16
NM_001198950.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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:

MYO16-AS1 (HGNC:):

MYO16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02846533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3 linkuse as main transcript	c.5378C>T	p.Ser1793Leu	missense_variant	34/35	ENST00000457511.7	NP_001185879.1	F8W883

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO16	ENST00000457511.7 linkuse as main transcript	c.5378C>T	p.Ser1793Leu	missense_variant	34/35	1	NM_001198950.3	ENSP00000401633.3	F8W883
MYO16	ENST00000356711.7 linkuse as main transcript	c.5312C>T	p.Ser1771Leu	missense_variant	34/35	1		ENSP00000349145.2	Q9Y6X6-1
MYO16-AS1	ENST00000439299.1 linkuse as main transcript	n.30-12292G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000370

AC:

AN:

251470

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000222

AC:

325

AN:

1461632

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

144

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000243

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000348

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000395

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000593

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

Oct 03, 2022

The c.5378C>T (p.S1793L) alteration is located in exon 34 (coding exon 34) of the MYO16 gene. This alteration results from a C to T substitution at nucleotide position 5378, causing the serine (S) at amino acid position 1793 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.16

M_CAP

Benign

0.081

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.7

D;.;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;.;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;.;D

Vest4

0.19

MVP

0.60

MPC

0.72

ClinPred

0.089

GERP RS

4.1

Varity_R

0.19

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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