15-71826716-T-G

Position:

• chr15-71826716-T-G

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.7511A>C​(p.Asn2504Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,614,152 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (73 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (54 hom.)
• Consequence: MYO9A NM_006901.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.18

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=0.001734823).
• BP6: Variant 15-71826716-T-G is Benign according to our data. Variant chr15-71826716-T-G is described in ClinVar as [Benign]. Clinvar id is 776922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9A	NM_006901.4	c.7511A>C	p.Asn2504Thr	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.7511A>C	p.Asn2504Thr	missense_variant	42/42	1	NM_006901.4	ENSP00000348349	P2
MYO9A	ENST00000561618.5	c.4061A>C	p.Asn1354Thr	missense_variant	19/19	1		ENSP00000457945
MYO9A	ENST00000564571.5	c.*316A>C		3_prime_UTR_variant	42/42	1		ENSP00000456192	A2
MYO9A	ENST00000568042.5	c.1256A>C	p.Asn419Thr	missense_variant	9/9	5		ENSP00000457407

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2424 AN: 152230 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00411 AC: 1033 AN: 251400 Hom.: 30 AF XY: 0.00305 AC XY: 414 AN XY: 135870

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00173 AC: 2526 AN: 1461804 Hom.: 54 Cov.: 31 AF XY: 0.00153 AC XY: 1110 AN XY: 727218

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000229

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.0159 AC: 2429 AN: 152348 Hom.: 73 Cov.: 32 AF XY: 0.0157 AC XY: 1171 AN XY: 74498

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00280 Hom.: 14

Bravo AF: 0.0181

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0507 AC: 223

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00504 AC: 612

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.66	.;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.22
Sift	Benign	0.17	T;.
Sift4G	Benign	0.79	T;T
Polyphen		0.48	P;P
Vest4		0.17
MVP		0.22
MPC		0.17
ClinPred		0.012	T
GERP RS		3.1
Varity_R		0.033
gMVP		0.078

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: rs112048853; hg19: chr15-72119057;