rs9301323

chr13-108806672-G-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.742-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,608,986 control chromosomes in the GnomAD database, including 403,828 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (32720 hom., cov: 31)
  • Exomes 𝑓: 0.71 (371108 hom.)
• Consequence: MYO16 NM_001198950.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002497
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.25

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 (BayesDel_noAF=-0.93).
• BP6: Variant 13-108806672-G-A is Benign according to our data. Variant chr13-108806672-G-A is described in ClinVar as [Benign]. Clinvar id is 3060009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO16	NM_001198950.3	c.742-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000457511.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO16	ENST00000457511.7	c.742-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001198950.3	A2
MYO16	ENST00000356711.7	c.676-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P2
MYO16	ENST00000251041.10	c.676-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
MYO16	ENST00000375857.6	n.62-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96866 AN: 151804 Hom.: 32696 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.670

GnomAD3 exomes AF: 0.724 AC: 181411 AN: 250636 Hom.: 66849 AF XY: 0.727 AC XY: 98499 AN XY: 135408

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.779

Gnomad SAS exome AF: 0.745

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.733

GnomAD4 exome AF: 0.711 AC: 1035864 AN: 1457064 Hom.: 371108 Cov.: 34 AF XY: 0.714 AC XY: 517378 AN XY: 725054

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.748

Gnomad4 FIN exome AF: 0.799

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.638 AC: 96911 AN: 151922 Hom.: 32720 Cov.: 31 AF XY: 0.645 AC XY: 47928 AN XY: 74276

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.672

Alfa AF: 0.679 Hom.: 17687

Bravo AF: 0.621

Asia WGS AF: 0.725 AC: 2520 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 17, 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
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.028
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs9301323; hg19: chr13-109459020; COSMIC: COSV51806603;