NM_006901.4:c.7462A>G

Variant names:

• chr15-71826765-T-C
• NM_006901.4:c.7462A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006901.4(MYO9A):​c.7462A>G​(p.Ile2488Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO9A NM_006901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07438266).

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.7462A>G	p.Ile2488Val	missense	Exon 42 of 42	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.7462A>G	p.Ile2488Val	missense	Exon 42 of 42	ENSP00000348349.5	B2RTY4-1
	MYO9A	ENST00000561618.5	TSL:1	c.4009A>G	p.Ile1337Val	missense	Exon 19 of 19	ENSP00000457945.1	H3BV44
	MYO9A	ENST00000564571.5	TSL:1	c.*267A>G		3_prime_UTR	Exon 42 of 42	ENSP00000456192.1	H3BRD5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0058	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.074	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.070	N
REVEL	Uncertain	0.34
Sift	Benign	0.16	T
Sift4G	Benign	0.55	T
Polyphen		0.14	B
Vest4		0.12
MutPred		0.14		Loss of catalytic residue at I2488 (P = 0.0492)
MVP		0.29
MPC		0.10
ClinPred		0.47	T
GERP RS		5.3
Varity_R		0.048
gMVP		0.098
Mutation Taster		=83/17	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

hg19: chr15-72119106;