15-71827003-C-G

Position:

• chr15-71827003-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006901.4(MYO9A):​c.7224G>C​(p.Lys2408Asn) 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. 13/21 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: 1.21

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=0.17199835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9A	NM_006901.4	c.7224G>C	p.Lys2408Asn	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.7224G>C	p.Lys2408Asn	missense_variant	42/42	1	NM_006901.4	ENSP00000348349	P2
MYO9A	ENST00000561618.5	c.3774G>C	p.Lys1258Asn	missense_variant	19/19	1		ENSP00000457945
MYO9A	ENST00000564571.5	c.*29G>C		3_prime_UTR_variant	42/42	1		ENSP00000456192	A2
MYO9A	ENST00000568042.5	c.969G>C	p.Lys323Asn	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

Myasthenic syndrome, congenital, 24, presynaptic Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	0.074
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	.;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	-0.0023	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.92	D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.067	T;T
Polyphen		0.80	P;P
Vest4		0.23
MutPred		0.16		Loss of methylation at K2408 (P = 0.0071);Loss of methylation at K2408 (P = 0.0071);
MVP		0.14
MPC		0.50
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.24

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: chr15-72119344;