15-71826765-T-C

Position:

• chr15-71826765-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9A	NM_006901.4	c.7462A>G	p.Ile2488Val	missense_variant	42/42	ENST00000356056.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9A	ENST00000356056.10	c.7462A>G	p.Ile2488Val	missense_variant	42/42	1	NM_006901.4	P2
MYO9A	ENST00000561618.5	c.4012A>G	p.Ile1338Val	missense_variant	19/19	1
MYO9A	ENST00000564571.5	c.*267A>G		3_prime_UTR_variant	42/42	1		A2
MYO9A	ENST00000568042.5	c.1207A>G	p.Ile403Val	missense_variant	9/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.7462A>G (p.I2488V) alteration is located in exon 42 (coding exon 41) of the MYO9A gene. This alteration results from a A to G substitution at nucleotide position 7462, causing the isoleucine (I) at amino acid position 2488 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.074	T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.070	N;.
REVEL	Uncertain	0.34
Sift	Benign	0.16	T;.
Sift4G	Benign	0.55	T;T
Polyphen		0.14	B;B
Vest4		0.12
MutPred		0.14		Loss of catalytic residue at I2488 (P = 0.0492);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-72119106;