15-71826660-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006901.4(MYO9A):​c.7567G>T​(p.Gly2523Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MYO9A
NM_006901.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.25454038).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO9ANM_006901.4 linkc.7567G>T p.Gly2523Cys missense_variant Exon 42 of 42 ENST00000356056.10 NP_008832.2 B2RTY4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO9AENST00000356056.10 linkc.7567G>T p.Gly2523Cys missense_variant Exon 42 of 42 1 NM_006901.4 ENSP00000348349.5 B2RTY4-1
MYO9AENST00000561618.5 linkc.4114G>T p.Gly1372Cys missense_variant Exon 19 of 19 1 ENSP00000457945.1 H3BV44
MYO9AENST00000564571 linkc.*372G>T 3_prime_UTR_variant Exon 42 of 42 1 ENSP00000456192.1 H3BRD5
MYO9AENST00000568042.5 linkc.1309G>T p.Gly437Cys missense_variant Exon 9 of 9 5 ENSP00000457407.1 H3BU05

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
Mar 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.7567G>T (p.G2523C) alteration is located in exon 42 (coding exon 41) of the MYO9A gene. This alteration results from a G to T substitution at nucleotide position 7567, causing the glycine (G) at amino acid position 2523 to be replaced by a cysteine (C). 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
0.14
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.025
T;T
Eigen
Benign
0.13
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.83
.;T
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-0.29
T
MutationAssessor
Benign
2.0
M;M
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.5
N;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.99
D;D
Vest4
0.31
MutPred
0.28
Gain of catalytic residue at M2521 (P = 5e-04);Gain of catalytic residue at M2521 (P = 5e-04);
MVP
0.18
MPC
0.41
ClinPred
0.85
D
GERP RS
3.0
Varity_R
0.16
gMVP
0.29

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: chr15-72119001; API