13-108727458-G-T

Variant names:

• chr13-108727458-G-T
• rs766497298
• NM_001198950.3:c.382G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001198950.3(MYO16):​c.382G>T​(p.Ala128Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: MYO16 NM_001198950.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.64
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29300833).

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.382G>T	p.Ala128Ser	missense	Exon 4 of 35	NP_001185879.1	F8W883
	MYO16	NM_015011.3		c.316G>T	p.Ala106Ser	missense	Exon 4 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.382G>T	p.Ala128Ser	missense	Exon 4 of 35	ENSP00000401633.3	F8W883
	MYO16	ENST00000356711.7	TSL:1	c.316G>T	p.Ala106Ser	missense	Exon 4 of 35	ENSP00000349145.2	Q9Y6X6-1
	MYO16	ENST00000251041.10	TSL:5	c.316G>T	p.Ala106Ser	missense	Exon 4 of 25	ENSP00000251041.5	Q9Y6X6-3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151978 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251130 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461558 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 727094

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000447 AC: 2 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111784

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151978 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74216

African (AFR) AF: 0.00 AC: 0 AN: 41342

American (AMR) AF: 0.0000656 AC: 1 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

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	0.097
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T
Eigen	Benign	0.060
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.095	N
PhyloP100		5.6
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.037	D
Sift4G	Uncertain	0.013	D
Polyphen		0.46	P
Vest4		0.25
MutPred		0.56		Loss of catalytic residue at A106 (P = 0.0613)
MVP		0.36
MPC		0.44
ClinPred		0.84	D
GERP RS		4.7
Varity_R		0.18
gMVP		0.37
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs766497298; hg19: chr13-109379806;