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GeneBe

15-71826665-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.323
Variant links:
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]

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ACMG classification

Classification made for transcript

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 UniProt
MYO9ANM_006901.4 linkuse as main transcriptc.7562T>G p.Met2521Arg missense_variant 42/42 ENST00000356056.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYO9AENST00000356056.10 linkuse as main transcriptc.7562T>G p.Met2521Arg missense_variant 42/421 NM_006901.4 P2B2RTY4-1
MYO9AENST00000561618.5 linkuse as main transcriptc.4112T>G p.Met1371Arg missense_variant 19/191
MYO9AENST00000564571.5 linkuse as main transcriptc.*367T>G 3_prime_UTR_variant 42/421 A2
MYO9AENST00000568042.5 linkuse as main transcriptc.1307T>G p.Met436Arg missense_variant 9/95

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
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 05, 2023The 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
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; API