chr13-109179568-C-G

Position:

• chr13-109179568-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198950.3(MYO16):​c.5350C>G​(p.Arg1784Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0310

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]

MYO16-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10827491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.5350C>G	p.Arg1784Gly	missense_variant	34/35	ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.5350C>G	p.Arg1784Gly	missense_variant	34/35	1	NM_001198950.3	ENSP00000401633.3
MYO16	ENST00000356711.7	c.5284C>G	p.Arg1762Gly	missense_variant	34/35	1		ENSP00000349145.2
MYO16-AS1	ENST00000439299.1	n.30-12264G>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.5350C>G (p.R1784G) alteration is located in exon 34 (coding exon 34) of the MYO16 gene. This alteration results from a C to G substitution at nucleotide position 5350, causing the arginine (R) at amino acid position 1784 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.5
DANN	Benign	0.90
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	2.0	M;.;M
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.83	P;.;P
Vest4		0.27
MutPred		0.54		Gain of glycosylation at S1761 (P = 0.0331);.;Gain of glycosylation at S1761 (P = 0.0331);
MVP		0.31
MPC		0.78
ClinPred		0.46	T
GERP RS		-2.1
Varity_R		0.15
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1345261475; hg19: chr13-109831916;