15-71853387-A-T

Variant names:

• chr15-71853387-A-T
• rs6494973
• NM_006901.4:c.6346+990T>A

Variant summary

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

The NM_006901.4(MYO9A):​c.6346+990T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,098 control chromosomes in the GnomAD database, including 20,717 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 0.45 (20717 hom., cov: 32)
• Consequence: MYO9A NM_006901.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 5 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9A	NM_006901.4	c.6346+990T>A		intron_variant	Intron 35 of 41	ENST00000356056.10	NP_008832.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9A	ENST00000356056.10	c.6346+990T>A		intron_variant	Intron 35 of 41	1	NM_006901.4	ENSP00000348349.5
MYO9A	ENST00000564571.5	c.6346+990T>A		intron_variant	Intron 35 of 41	1		ENSP00000456192.1
MYO9A	ENST00000561618.5	c.2893+990T>A		intron_variant	Intron 12 of 18	1		ENSP00000457945.1
MYO9A	ENST00000568042.5	c.34+990T>A		intron_variant	Intron 1 of 8	5		ENSP00000457407.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68910 AN: 151980 Hom.: 20656 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.454 AC: 69039 AN: 152098 Hom.: 20717 Cov.: 32 AF XY: 0.451 AC XY: 33506 AN XY: 74340

African (AFR) AF: 0.847 AC: 35188 AN: 41526

American (AMR) AF: 0.377 AC: 5755 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 778 AN: 3464

East Asian (EAS) AF: 0.638 AC: 3289 AN: 5158

South Asian (SAS) AF: 0.331 AC: 1596 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3052 AN: 10580

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18173 AN: 67968

Other (OTH) AF: 0.417 AC: 882 AN: 2114

Alfa AF: 0.352 Hom.: 1502

Bravo AF: 0.480

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.3
DANN	Benign	0.91
PhyloP100		-0.14
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: rs6494973; hg19: chr15-72145728;