13-108666025-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001198950.3(MYO16):c.168C>T(p.Arg56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,614,012 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (210 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (168 hom.)
• Consequence: MYO16 NM_001198950.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-108666025-C-T is Benign according to our data. Variant chr13-108666025-C-T is described in ClinVar as [Benign]. Clinvar id is 785448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO16	NM_001198950.3	c.168C>T	p.Arg56=	synonymous_variant	2/35	ENST00000457511.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO16	ENST00000457511.7	c.168C>T	p.Arg56=	synonymous_variant	2/35	1	NM_001198950.3	A2
MYO16	ENST00000356711.7	c.102C>T	p.Arg34=	synonymous_variant	2/35	1		P2
MYO16	ENST00000251041.10	c.102C>T	p.Arg34=	synonymous_variant	2/25	5

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4413 AN: 152082 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.00777 AC: 1952 AN: 251062 Hom.: 89 AF XY: 0.00567 AC XY: 769 AN XY: 135682

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00396

Gnomad ASJ exome AF: 0.00626

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000476

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00317 AC: 4635 AN: 1461814 Hom.: 168 Cov.: 31 AF XY: 0.00282 AC XY: 2049 AN XY: 727208

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00459

Gnomad4 ASJ exome AF: 0.00639

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000317

Gnomad4 OTH exome AF: 0.00647

GnomAD4 genome AF: 0.0290 AC: 4419 AN: 152198 Hom.: 210 Cov.: 32 AF XY: 0.0275 AC XY: 2049 AN XY: 74406

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0140 Hom.: 39

Bravo AF: 0.0325

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.46
Dann	Benign	0.65

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: rs61745206; hg19: chr13-109318373; COSMIC: COSV51781559;