rs3825491

Positions:

• chr13-109009011-C-A
• chr13-109009011-C-G
• chr13-109009011-C-T

Variant summary

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

The NM_001198950.3(MYO16):​c.2557C>A​(p.Pro853Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

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.2557C>A	p.Pro853Thr	missense_variant	22/35	ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.2557C>A	p.Pro853Thr	missense_variant	22/35	1	NM_001198950.3	ENSP00000401633.3
MYO16	ENST00000356711.7	c.2491C>A	p.Pro831Thr	missense_variant	22/35	1		ENSP00000349145.2
MYO16	ENST00000251041.10	c.2491C>A	p.Pro831Thr	missense_variant	22/25	5		ENSP00000251041.5
MYO16	ENST00000375857.6	n.1877C>A		non_coding_transcript_exon_variant	17/22	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T;T;.;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Benign	1.1	L;.;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D;.;D;D
REVEL	Uncertain	0.45
Sift	Benign	0.35	T;.;T;T
Sift4G	Benign	0.072	T;T;T;T
Polyphen		0.71	P;.;.;P
Vest4		0.43
MutPred		0.58		Gain of catalytic residue at P831 (P = 0.0672);.;Gain of catalytic residue at P831 (P = 0.0672);Gain of catalytic residue at P831 (P = 0.0672);
MVP		0.51
MPC		0.72
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.33
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3825491; hg19: chr13-109661359;