13-108821598-G-A

Variant names:

• chr13-108821598-G-A
• rs17393344
• NM_001198950.3:c.943+1186G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001198950.3(MYO16):​c.943+1186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 152,240 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.024 (61 hom., cov: 33)
• Consequence: MYO16 NM_001198950.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0241 (3676/152240) while in subpopulation NFE AF = 0.0402 (2737/68016). AF 95% confidence interval is 0.039. There are 61 homozygotes in GnomAd4. There are 1663 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	NM_001198950.3	MANE Select	c.943+1186G>A		intron	N/A	NP_001185879.1
	MYO16	NM_015011.3		c.877+1186G>A		intron	N/A	NP_055826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	ENST00000457511.7	TSL:1 MANE Select	c.943+1186G>A		intron	N/A	ENSP00000401633.3
	MYO16	ENST00000356711.7	TSL:1	c.877+1186G>A		intron	N/A	ENSP00000349145.2
	MYO16	ENST00000251041.10	TSL:5	c.877+1186G>A		intron	N/A	ENSP00000251041.5

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3676 AN: 152122 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0241 AC: 3676 AN: 152240 Hom.: 61 Cov.: 33 AF XY: 0.0223 AC XY: 1663 AN XY: 74438

African (AFR) AF: 0.00705 AC: 293 AN: 41540

American (AMR) AF: 0.0284 AC: 433 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10612

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0402 AC: 2737 AN: 68016

Other (OTH) AF: 0.0307 AC: 65 AN: 2116

Alfa AF: 0.0326 Hom.: 179

Bravo AF: 0.0252

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.60
PhyloP100		0.011
Mutation Taster		=100/0	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: rs17393344; hg19: chr13-109473946;