13-109165018-C-T

Position:

• chr13-109165018-C-T

Variant summary

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

The NM_001198950.3(MYO16):​c.5282C>T​(p.Ser1761Phe) 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. 12/21 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: 2.87

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:39913): (MYO16 antisense RNA 1)

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=0.2085453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.5282C>T	p.Ser1761Phe	missense_variant	33/35	ENST00000457511.7	NP_001185879.1
MYO16-AS1	NR_047700.1	n.361-927G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.5282C>T	p.Ser1761Phe	missense_variant	33/35	1	NM_001198950.3	ENSP00000401633	A2
MYO16	ENST00000356711.7	c.5216C>T	p.Ser1739Phe	missense_variant	33/35	1		ENSP00000349145	P2
MYO16-AS1	ENST00000439299.1	n.391-927G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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

Jun 05, 2023

The c.5282C>T (p.S1761F) alteration is located in exon 33 (coding exon 33) of the MYO16 gene. This alteration results from a C to T substitution at nucleotide position 5282, causing the serine (S) at amino acid position 1761 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	0.0050
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.1	M;.;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D;.;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		0.88	P;.;P
Vest4		0.46
MutPred		0.23		Loss of phosphorylation at S1739 (P = 0.0554);.;Loss of phosphorylation at S1739 (P = 0.0554);
MVP		0.54
MPC		1.4
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.25
gMVP		0.16

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: rs1878578283; hg19: chr13-109817366;