15-71827228-C-T

Position:

• chr15-71827228-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006901.4(MYO9A):​c.7184-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 152,214 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (228 hom., cov: 32)
• Consequence: MYO9A NM_006901.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.66

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-71827228-C-T is Benign according to our data. Variant chr15-71827228-C-T is described in ClinVar as [Benign]. Clinvar id is 1269225.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO9A	NM_006901.4	c.7184-185G>A		intron_variant		ENST00000356056.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO9A	ENST00000356056.10	c.7184-185G>A		intron_variant		1	NM_006901.4	P2
MYO9A	ENST00000561618.5	c.3733-185G>A		intron_variant		1
MYO9A	ENST00000564571.5	c.7184-189G>A		intron_variant		1		A2
MYO9A	ENST00000568042.5	c.928-185G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7656 AN: 152096 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0503 AC: 7658 AN: 152214 Hom.: 228 Cov.: 32 AF XY: 0.0495 AC XY: 3682 AN XY: 74406

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0588 Hom.: 359

Bravo AF: 0.0475

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.76

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: rs10518970; hg19: chr15-72119569;