rs9301323

Variant names:

• chr13-108806672-G-A
• rs9301323
• NM_001198950.3:c.742-7G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001198950.3(MYO16):​c.742-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,608,986 control chromosomes in the GnomAD database, including 403,828 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.64 (32720 hom., cov: 31)
  • Exomes 𝑓: 0.71 (371108 hom.)
• Consequence: MYO16 NM_001198950.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002497
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.25
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 13-108806672-G-A is Benign according to our data. Variant chr13-108806672-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060009.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

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.742-7G>A		splice_region intron	N/A	NP_001185879.1
	MYO16	NM_015011.3		c.676-7G>A		splice_region intron	N/A	NP_055826.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO16	ENST00000457511.7	TSL:1 MANE Select	c.742-7G>A		splice_region intron	N/A	ENSP00000401633.3
	MYO16	ENST00000356711.7	TSL:1	c.676-7G>A		splice_region intron	N/A	ENSP00000349145.2
	MYO16	ENST00000251041.10	TSL:5	c.676-7G>A		splice_region intron	N/A	ENSP00000251041.5

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96866 AN: 151804 Hom.: 32696 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.670

GnomAD2 exomes AF: 0.724 AC: 181411 AN: 250636 AF XY: 0.727

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.779

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.718

Gnomad OTH exome AF: 0.733

GnomAD4 exome AF: 0.711 AC: 1035864 AN: 1457064 Hom.: 371108 Cov.: 34 AF XY: 0.714 AC XY: 517378 AN XY: 725054

African (AFR) AF: 0.381 AC: 12702 AN: 33378

American (AMR) AF: 0.782 AC: 34915 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 19451 AN: 26012

East Asian (EAS) AF: 0.759 AC: 30053 AN: 39596

South Asian (SAS) AF: 0.748 AC: 64329 AN: 85954

European-Finnish (FIN) AF: 0.799 AC: 42526 AN: 53252

Middle Eastern (MID) AF: 0.747 AC: 4284 AN: 5734

European-Non Finnish (NFE) AF: 0.709 AC: 785501 AN: 1108332

Other (OTH) AF: 0.700 AC: 42103 AN: 60170

GnomAD4 genome AF: 0.638 AC: 96911 AN: 151922 Hom.: 32720 Cov.: 31 AF XY: 0.645 AC XY: 47928 AN XY: 74276

African (AFR) AF: 0.395 AC: 16327 AN: 41350

American (AMR) AF: 0.706 AC: 10775 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2612 AN: 3464

East Asian (EAS) AF: 0.773 AC: 3988 AN: 5162

South Asian (SAS) AF: 0.748 AC: 3598 AN: 4812

European-Finnish (FIN) AF: 0.808 AC: 8546 AN: 10578

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.717 AC: 48748 AN: 67984

Other (OTH) AF: 0.672 AC: 1421 AN: 2116

Alfa AF: 0.678 Hom.: 25521

Bravo AF: 0.621

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYO16-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.028
DANN	Benign	0.38
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs9301323; hg19: chr13-109459020; COSMIC: COSV51806603;