15-71827050-C-CA

Variant names:

• chr15-71827050-C-CA
• rs748769280
• NM_006901.4:c.7184-8dupT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_006901.4(MYO9A):​c.7184-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,541,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: MYO9A NM_006901.4 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.15
• Publications: 0 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: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• presynaptic congenital myasthenic syndrome

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

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 15-71827050-C-CA is Benign according to our data. Variant chr15-71827050-C-CA is described in ClinVar as Likely_benign. ClinVar VariationId is 3033672.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006901.4. 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
	MYO9A	NM_006901.4	MANE Select	c.7184-8dupT		splice_region intron	N/A	NP_008832.2	B2RTY4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO9A	ENST00000356056.10	TSL:1 MANE Select	c.7184-8_7184-7insT		splice_region intron	N/A	ENSP00000348349.5	B2RTY4-1
	MYO9A	ENST00000564571.5	TSL:1	c.7184-12_7184-11insT		intron	N/A	ENSP00000456192.1	H3BRD5
	MYO9A	ENST00000561618.5	TSL:1	c.3731-8_3731-7insT		splice_region intron	N/A	ENSP00000457945.1	H3BV44

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000138 AC: 26 AN: 187730 AF XY: 0.000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000674

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000132 AC: 184 AN: 1389966 Hom.: 0 Cov.: 29 AF XY: 0.000119 AC XY: 82 AN XY: 687244

African (AFR) AF: 0.0000329 AC: 1 AN: 30436

American (AMR) AF: 0.000547 AC: 17 AN: 31074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21774

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39242

South Asian (SAS) AF: 0.00 AC: 0 AN: 74760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.000147 AC: 159 AN: 1081998

Other (OTH) AF: 0.000105 AC: 6 AN: 57292

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74202

African (AFR) AF: 0.0000483 AC: 2 AN: 41382

American (AMR) AF: 0.000197 AC: 3 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000831

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYO9A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs748769280; hg19: chr15-72119391;