13-108727441-G-T

Position:

• chr13-108727441-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001198950.3(MYO16):​c.365G>T​(p.Cys122Phe) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO16 NM_001198950.3 missense, splice_region
• Scores: Splicing: ADA: 0.9200
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.61

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.365G>T	p.Cys122Phe	missense_variant, splice_region_variant	4/35	ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.365G>T	p.Cys122Phe	missense_variant, splice_region_variant	4/35	1	NM_001198950.3	ENSP00000401633.3
MYO16	ENST00000356711.7	c.299G>T	p.Cys100Phe	missense_variant, splice_region_variant	4/35	1		ENSP00000349145.2
MYO16	ENST00000251041.10	c.299G>T	p.Cys100Phe	missense_variant, splice_region_variant	4/25	5		ENSP00000251041.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Feb 23, 2023

The c.365G>T (p.C122F) alteration is located in exon 4 (coding exon 4) of the MYO16 gene. This alteration results from a G to T substitution at nucleotide position 365, causing the cysteine (C) at amino acid position 122 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.4	L;.;L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.3	D;.;D;D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.82
MutPred		0.72		Loss of catalytic residue at H98 (P = 0.1315);.;Loss of catalytic residue at H98 (P = 0.1315);Loss of catalytic residue at H98 (P = 0.1315);
MVP		0.66
MPC		0.92
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.89
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-109379789;