rs911973

Positions:

• chr13-108785736-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (250 hom., cov: 33)
  • Exomes 𝑓: 0.042 (2746 hom.)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 3059259.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
MYO16	NM_001198950.3	c.609T>A	p.Asp203Glu	missense_variant	5/35	ENST00000457511.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO16	ENST00000457511.7	c.609T>A	p.Asp203Glu	missense_variant	5/35	1	NM_001198950.3	A2
MYO16	ENST00000356711.7	c.543T>A	p.Asp181Glu	missense_variant	5/35	1		P2
MYO16	ENST00000251041.10	c.543T>A	p.Asp181Glu	missense_variant	5/25	5
MYO16	ENST00000467639.1	n.613T>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5082 AN: 152218 Hom.: 249 Cov.: 33

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

GnomAD3 exomes AF: 0.0528 AC: 12653 AN: 239740 Hom.: 829 AF XY: 0.0564 AC XY: 7313 AN XY: 129600

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 SAS exome AF: 0.131

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.: 27 AF XY: 0.0441 AC XY: 31725 AN XY: 719240

Gnomad4 AFR exome AF: 0.00594

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0462

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.00837

Gnomad4 NFE exome AF: 0.0306

Gnomad4 OTH exome AF: 0.0528

GnomAD4 genome AF: 0.0333 AC: 5080 AN: 152336 Hom.: 250 Cov.: 33 AF XY: 0.0355 AC XY: 2641 AN XY: 74494

Gnomad4 AFR AF: 0.00782

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.00828

Gnomad4 NFE AF: 0.0290

Gnomad4 OTH AF: 0.0340

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: 49

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: criteria provided, single submitter

Submissions by phenotype

MYO16-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

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	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.3
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	N
MetaRNN	Benign	0.0016	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N;N
MutationTaster	Benign	0.87	P;P;P
PrimateAI	Benign	0.41	T
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	T
GERP RS		2.7
Varity_R		0.041
gMVP		0.12

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

Other links and lift over

dbSNP: rs911973; hg19: chr13-109438084; COSMIC: COSV51796081;