rs12050794

Variant names:

• chr15-71877125-G-A
• rs12050794
• NM_006901.4:c.5931+915C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-71877125-G-A
• chr15-71877125-G-C
• chr15-71877125-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000356056.10(MYO9A):​c.5931+915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,050 control chromosomes in the GnomAD database, including 27,523 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 0.54 (27523 hom., cov: 32)
• Consequence: MYO9A ENST00000356056.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 15 publications found

Genes affected

MYO9A (HGNC:7608): (myosin IXA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with Bardet-Biedl Syndrome. [provided by RefSeq, Dec 2011]

MYO9A Gene-Disease associations (from GenCC):

• myasthenic syndrome, congenital, 24, presynaptic

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arthrogryposis syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356056.10. 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
	MYO9A	NM_006901.4	MANE Select	c.5931+915C>T		intron	N/A	NP_008832.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9A	ENST00000356056.10	TSL:1 MANE Select	c.5931+915C>T		intron	N/A	ENSP00000348349.5
	MYO9A	ENST00000564571.5	TSL:1	c.5931+915C>T		intron	N/A	ENSP00000456192.1
	MYO9A	ENST00000561618.5	TSL:1	c.2478+915C>T		intron	N/A	ENSP00000457945.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82588 AN: 151928 Hom.: 27533 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.543 AC: 82575 AN: 152050 Hom.: 27523 Cov.: 32 AF XY: 0.546 AC XY: 40580 AN XY: 74308

African (AFR) AF: 0.152 AC: 6296 AN: 41460

American (AMR) AF: 0.622 AC: 9504 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2681 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1566 AN: 5164

South Asian (SAS) AF: 0.666 AC: 3207 AN: 4818

European-Finnish (FIN) AF: 0.713 AC: 7520 AN: 10552

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49696 AN: 67996

Other (OTH) AF: 0.579 AC: 1225 AN: 2114

Alfa AF: 0.517 Hom.: 11598

Bravo AF: 0.517

Asia WGS AF: 0.408 AC: 1418 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.59
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs12050794; hg19: chr15-72169466;