13-108665961-T-C

Variant names:

• chr13-108665961-T-C
• rs764834954
• NM_001198950.3:c.104T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 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.104T>C	p.Leu35Pro	missense	Exon 2 of 35	NP_001185879.1	F8W883
	MYO16	NM_015011.3		c.38T>C	p.Leu13Pro	missense	Exon 2 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.104T>C	p.Leu35Pro	missense	Exon 2 of 35	ENSP00000401633.3	F8W883
	MYO16	ENST00000356711.7	TSL:1	c.38T>C	p.Leu13Pro	missense	Exon 2 of 35	ENSP00000349145.2	Q9Y6X6-1
	MYO16	ENST00000251041.10	TSL:5	c.38T>C	p.Leu13Pro	missense	Exon 2 of 25	ENSP00000251041.5	Q9Y6X6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.25		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
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs764834954; hg19: chr13-109318309;