13-108666022-G-A

Variant names:

• chr13-108666022-G-A
• rs117770145
• NM_001198950.3:c.165G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001198950.3(MYO16):​c.165G>A​(p.Glu55Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,614,144 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (90 hom.)
• Consequence: MYO16 NM_001198950.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.528

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 13-108666022-G-A is Benign according to our data. Variant chr13-108666022-G-A is described in ClinVar as [Benign]. Clinvar id is 790871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.528 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00209 (318/152328) while in subpopulation SAS AF= 0.0325 (157/4832). AF 95% confidence interval is 0.0283. There are 4 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.165G>A	p.Glu55Glu	synonymous_variant	Exon 2 of 35	ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.165G>A	p.Glu55Glu	synonymous_variant	Exon 2 of 35	1	NM_001198950.3	ENSP00000401633.3
MYO16	ENST00000356711.7	c.99G>A	p.Glu33Glu	synonymous_variant	Exon 2 of 35	1		ENSP00000349145.2
MYO16	ENST00000251041.10	c.99G>A	p.Glu33Glu	synonymous_variant	Exon 2 of 25	5		ENSP00000251041.5

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 320 AN: 152210 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00539 AC: 1354 AN: 251032 Hom.: 27 AF XY: 0.00713 AC XY: 967 AN XY: 135668

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00332 AC: 4860 AN: 1461816 Hom.: 90 Cov.: 31 AF XY: 0.00439 AC XY: 3195 AN XY: 727208

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.00381

GnomAD4 genome AF: 0.00209 AC: 318 AN: 152328 Hom.: 4 Cov.: 32 AF XY: 0.00263 AC XY: 196 AN XY: 74484

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00205 Hom.: 1

Bravo AF: 0.00133

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

MYO16-related disorder Benign:1

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.54

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: rs117770145; hg19: chr13-109318370;