15-71827899-T-C

Position:

• chr15-71827899-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006901.4(MYO9A):​c.7168A>G​(p.Ile2390Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,613,290 control chromosomes in the GnomAD database, including 764 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0060 (62 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (702 hom.)
• Consequence: MYO9A NM_006901.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0130

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013604462).
• BP6: Variant 15-71827899-T-C is Benign according to our data. Variant chr15-71827899-T-C is described in ClinVar as [Benign]. Clinvar id is 1252587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9A	NM_006901.4	c.7168A>G	p.Ile2390Val	missense_variant	41/42	ENST00000356056.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9A	ENST00000356056.10	c.7168A>G	p.Ile2390Val	missense_variant	41/42	1	NM_006901.4	P2

Frequencies

GnomAD3 genomes AF: 0.00608 AC: 925 AN: 152210 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.0125 AC: 3135 AN: 250452 Hom.: 202 AF XY: 0.0112 AC XY: 1513 AN XY: 135316

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.0108

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.00253

Gnomad FIN exome AF: 0.000833

Gnomad NFE exome AF: 0.000362

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00585 AC: 8549 AN: 1460962 Hom.: 702 Cov.: 31 AF XY: 0.00572 AC XY: 4156 AN XY: 726758

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.00951

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.00239

Gnomad4 FIN exome AF: 0.000730

Gnomad4 NFE exome AF: 0.000239

Gnomad4 OTH exome AF: 0.00731

GnomAD4 genome AF: 0.00605 AC: 921 AN: 152328 Hom.: 62 Cov.: 32 AF XY: 0.00670 AC XY: 499 AN XY: 74498

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00239 Hom.: 9

Bravo AF: 0.00686

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000910 AC: 4

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.0119 AC: 1449

Asia WGS AF: 0.0540 AC: 187 AN: 3478

EpiCase AF: 0.000546

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MYO9A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.30
DANN	Benign	0.66
DEOGEN2	Benign	0.012	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.14	N
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;L
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.25	N;N;.
REVEL	Benign	0.24
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.062
MPC		0.083
ClinPred		0.00072	T
GERP RS		-6.5
Varity_R		0.017
gMVP		0.089

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

LitVar

Other links and lift over

dbSNP: rs2291280; hg19: chr15-72120240; COSMIC: COSV61848343; COSMIC: COSV61848343;