rs12902421

Variant names:

• chr15-71869062-T-C
• rs12902421
• NM_006901.4:c.5980-6451A>G

Variant summary

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

The NM_006901.4(MYO9A):​c.5980-6451A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 132,742 control chromosomes in the GnomAD database, including 16 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 0.014 (16 hom., cov: 32)
• Consequence: MYO9A NM_006901.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 30 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=-0.95).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0144 (1914/132742) while in subpopulation EAS AF = 0.0369 (125/3390). AF 95% confidence interval is 0.0316. There are 16 homozygotes in GnomAd4. There are 874 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,Unknown,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9A	NM_006901.4	c.5980-6451A>G		intron_variant	Intron 32 of 41	ENST00000356056.10	NP_008832.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9A	ENST00000356056.10	c.5980-6451A>G		intron_variant	Intron 32 of 41	1	NM_006901.4	ENSP00000348349.5
MYO9A	ENST00000564571.5	c.5980-6451A>G		intron_variant	Intron 32 of 41	1		ENSP00000456192.1
MYO9A	ENST00000561618.5	c.2527-6451A>G		intron_variant	Intron 9 of 18	1		ENSP00000457945.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 1909 AN: 132654 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00548

Gnomad AMI AF: 0.0977

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.00680

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0175

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

GnomAD4 genome AF: 0.0144 AC: 1914 AN: 132742 Hom.: 16 Cov.: 32 AF XY: 0.0135 AC XY: 874 AN XY: 64824

African (AFR) AF: 0.00546 AC: 176 AN: 32230

American (AMR) AF: 0.0112 AC: 150 AN: 13356

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 20 AN: 3300

East Asian (EAS) AF: 0.0369 AC: 125 AN: 3390

South Asian (SAS) AF: 0.0101 AC: 43 AN: 4258

European-Finnish (FIN) AF: 0.00520 AC: 50 AN: 9616

Middle Eastern (MID) AF: 0.00730 AC: 2 AN: 274

European-Non Finnish (NFE) AF: 0.0193 AC: 1225 AN: 63608

Other (OTH) AF: 0.0207 AC: 38 AN: 1840

Alfa AF: 0.0169 Hom.: 85

Bravo AF: 0.0128

Asia WGS AF: 0.0320 AC: 110 AN: 3370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.65
PhyloP100		-0.077
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: rs12902421; hg19: chr15-72161403;