13-108665961-T-C

Position:

• chr13-108665961-T-C

Variant summary

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

The NM_001198950.3(MYO16):​c.104T>C​(p.Leu35Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.104T>C	p.Leu35Pro	missense_variant	2/35	ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.104T>C	p.Leu35Pro	missense_variant	2/35	1	NM_001198950.3	ENSP00000401633.3
MYO16	ENST00000356711.7	c.38T>C	p.Leu13Pro	missense_variant	2/35	1		ENSP00000349145.2
MYO16	ENST00000251041.10	c.38T>C	p.Leu13Pro	missense_variant	2/25	5		ENSP00000251041.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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 16, 2023

The c.104T>C (p.L35P) alteration is located in exon 2 (coding exon 2) of the MYO16 gene. This alteration results from a T to C substitution at nucleotide position 104, causing the leucine (L) at amino acid position 35 to be replaced by a proline (P). 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	0.27
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0029	T;T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L;.;L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N;.;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.91
MutPred		0.25		Gain of disorder (P = 0.0172);.;Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);
MVP		0.46
MPC		0.92
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.72

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: rs764834954; hg19: chr13-109318309;