rs4578513

Positions:

• chr13-108726658-G-A
• chr13-108726658-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001198950.3(MYO16):​c.364-782G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,744 control chromosomes in the GnomAD database, including 5,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5127 hom., cov: 31)
• Consequence: MYO16 NM_001198950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.364-782G>A		intron_variant		ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.364-782G>A		intron_variant		1	NM_001198950.3	ENSP00000401633	A2
MYO16	ENST00000356711.7	c.298-782G>A		intron_variant		1		ENSP00000349145	P2
MYO16	ENST00000251041.10	c.298-782G>A		intron_variant		5		ENSP00000251041

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35023 AN: 151632 Hom.: 5118 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35067 AN: 151744 Hom.: 5127 Cov.: 31 AF XY: 0.227 AC XY: 16796 AN XY: 74126

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0488

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.231

Alfa AF: 0.170 Hom.: 3410

Bravo AF: 0.246

Asia WGS AF: 0.103 AC: 361 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.62
DANN	Benign	0.63

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: rs4578513; hg19: chr13-109379006;