15-71826665-A-C

Position:

• chr15-71826665-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006901.4(MYO9A):​c.7562T>G​(p.Met2521Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.323

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04072112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9A	NM_006901.4	c.7562T>G	p.Met2521Arg	missense_variant	42/42	ENST00000356056.10	NP_008832.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9A	ENST00000356056.10	c.7562T>G	p.Met2521Arg	missense_variant	42/42	1	NM_006901.4	ENSP00000348349	P2
MYO9A	ENST00000561618.5	c.4112T>G	p.Met1371Arg	missense_variant	19/19	1		ENSP00000457945
MYO9A	ENST00000564571.5	c.*367T>G		3_prime_UTR_variant	42/42	1		ENSP00000456192	A2
MYO9A	ENST00000568042.5	c.1307T>G	p.Met436Arg	missense_variant	9/9	5		ENSP00000457407

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

Apr 05, 2023

The c.7562T>G (p.M2521R) alteration is located in exon 42 (coding exon 41) of the MYO9A gene. This alteration results from a T to G substitution at nucleotide position 7562, causing the methionine (M) at amino acid position 2521 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	5.7
DANN	Benign	0.73
DEOGEN2	Benign	0.0061	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.16	N;.
REVEL	Benign	0.26
Sift	Benign	0.086	T;.
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.20		Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);
MVP		0.25
MPC		0.16
ClinPred		0.024	T
GERP RS		-3.9
Varity_R		0.14
gMVP		0.11

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: chr15-72119006;