Variant 15-71826982-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006901.4(MYO9A):c.7245G>T(p.Leu2415Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYO9A
NM_006901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0170

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]

MYO9A links:

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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=0.03314373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9A	NM_006901.4 linkuse as main transcript	c.7245G>T	p.Leu2415Phe	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 linkuse as main transcript	c.7245G>T	p.Leu2415Phe	missense_variant	42/42	1	NM_006901.4	ENSP00000348349	P2	B2RTY4-1
MYO9A	ENST00000561618.5 linkuse as main transcript	c.3795G>T	p.Leu1265Phe	missense_variant	19/19	1		ENSP00000457945
MYO9A	ENST00000564571.5 linkuse as main transcript	c.*50G>T		3_prime_UTR_variant	42/42	1		ENSP00000456192	A2
MYO9A	ENST00000568042.5 linkuse as main transcript	c.990G>T	p.Leu330Phe	missense_variant	9/9	5		ENSP00000457407

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460938

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.7245G>T (p.L2415F) 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 7245, causing the leucine (L) at amino acid position 2415 to be replaced by a phenylalanine (F). 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

0.081

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.76

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.83

N;.

REVEL

Benign

0.13

Sift

Benign

0.23

T;.

Sift4G

Benign

0.71

T;T

Polyphen

0.0010

B;B

Vest4

0.074

MutPred

0.18

Gain of methylation at K2414 (P = 0.0284);Gain of methylation at K2414 (P = 0.0284);

MVP

0.15

MPC

0.11

ClinPred

0.030

GERP RS

0.16

Varity_R

0.029

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over