Variant 13-109164925-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001198950.3(MYO16):c.5189G>A(p.Ser1730Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MYO16
NM_001198950.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.115

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:39913): (MYO16 antisense RNA 1)

MYO16-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04907781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3 linkuse as main transcript	c.5189G>A	p.Ser1730Asn	missense_variant	33/35	ENST00000457511.7	NP_001185879.1
MYO16-AS1	NR_047700.1 linkuse as main transcript	n.361-834C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7 linkuse as main transcript	c.5189G>A	p.Ser1730Asn	missense_variant	33/35	1	NM_001198950.3	ENSP00000401633	A2
MYO16	ENST00000356711.7 linkuse as main transcript	c.5123G>A	p.Ser1708Asn	missense_variant	33/35	1		ENSP00000349145	P2	Q9Y6X6-1
MYO16-AS1	ENST00000439299.1 linkuse as main transcript	n.391-834C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1433348

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 01, 2023

The c.5189G>A (p.S1730N) alteration is located in exon 33 (coding exon 33) of the MYO16 gene. This alteration results from a G to A substitution at nucleotide position 5189, causing the serine (S) at amino acid position 1730 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0038

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.021

M_CAP

Benign

0.035

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.78

N;.;N

REVEL

Benign

0.17

Sift

Benign

0.19

T;.;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.18

MutPred

0.13

Loss of phosphorylation at S1708 (P = 0.0219);.;Loss of phosphorylation at S1708 (P = 0.0219);

MVP

0.27

MPC

0.56

ClinPred

0.042

GERP RS

-1.2

Varity_R

0.057

gMVP

0.046

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over