chr13-109009011-C-A

Variant names:

• chr13-109009011-C-A
• rs3825491
• NM_001198950.3:c.2557C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P853A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 21 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198950.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	NM_001198950.3	MANE Select	c.2557C>A	p.Pro853Thr	missense	Exon 22 of 35	NP_001185879.1	F8W883
	MYO16	NM_015011.3		c.2491C>A	p.Pro831Thr	missense	Exon 22 of 35	NP_055826.1	Q9Y6X6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	ENST00000457511.7	TSL:1 MANE Select	c.2557C>A	p.Pro853Thr	missense	Exon 22 of 35	ENSP00000401633.3	F8W883
	MYO16	ENST00000356711.7	TSL:1	c.2491C>A	p.Pro831Thr	missense	Exon 22 of 35	ENSP00000349145.2	Q9Y6X6-1
	MYO16	ENST00000251041.10	TSL:5	c.2491C>A	p.Pro831Thr	missense	Exon 22 of 25	ENSP00000251041.5	Q9Y6X6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7878

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.9
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.45
Sift	Benign	0.35	T
Sift4G	Benign	0.072	T
Polyphen		0.71	P
Vest4		0.43
MutPred		0.58		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
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs3825491; hg19: chr13-109661359;