13-109009011-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001198950.3(MYO16):​c.2557C>T​(p.Pro853Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO16	NM_001198950.3	c.2557C>T	p.Pro853Ser	missense_variant	Exon 22 of 35	ENST00000457511.7	NP_001185879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO16	ENST00000457511.7	c.2557C>T	p.Pro853Ser	missense_variant	Exon 22 of 35	1	NM_001198950.3	ENSP00000401633.3
MYO16	ENST00000356711.7	c.2491C>T	p.Pro831Ser	missense_variant	Exon 22 of 35	1		ENSP00000349145.2
MYO16	ENST00000251041.10	c.2491C>T	p.Pro831Ser	missense_variant	Exon 22 of 25	5		ENSP00000251041.5
MYO16	ENST00000375857.6	n.1877C>T		non_coding_transcript_exon_variant	Exon 17 of 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	0.12
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	1.5	L;.;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;.;D;D
REVEL	Uncertain	0.47
Sift	Benign	0.22	T;.;T;T
Sift4G	Benign	0.076	T;T;T;T
Polyphen		0.99	D;.;.;D
Vest4		0.39
MutPred		0.68		Gain of disorder (P = 0.0812);.;Gain of disorder (P = 0.0812);Gain of disorder (P = 0.0812);
MVP		0.56
MPC		0.66
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.25
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;