11-77183190-G-T

Position:

• chr11-77183190-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000260.4(MYO7A):​c.3375+33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,543,576 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0045 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (38 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00446 (679/152218) while in subpopulation NFE AF= 0.00368 (250/68002). AF 95% confidence interval is 0.0033. There are 3 homozygotes in gnomad4. There are 445 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3375+33G>T		intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3375+33G>T		intron_variant		1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3375+33G>T		intron_variant		1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3342+33G>T		intron_variant		1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.918+33G>T		intron_variant		1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1215+33G>T		intron_variant				ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.00446 AC: 679 AN: 152100 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00464 AC: 706 AN: 152118 Hom.: 14 AF XY: 0.00412 AC XY: 333 AN XY: 80746

Gnomad AFR exome AF: 0.000383

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000176

Gnomad FIN exome AF: 0.0340

Gnomad NFE exome AF: 0.00272

Gnomad OTH exome AF: 0.00255

GnomAD4 exome AF: 0.00368 AC: 5123 AN: 1391358 Hom.: 38 Cov.: 28 AF XY: 0.00362 AC XY: 2484 AN XY: 686678

Gnomad4 AFR exome AF: 0.000382

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.0000398

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000266

Gnomad4 FIN exome AF: 0.0311

Gnomad4 NFE exome AF: 0.00320

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome AF: 0.00446 AC: 679 AN: 152218 Hom.: 3 Cov.: 33 AF XY: 0.00598 AC XY: 445 AN XY: 74430

Gnomad4 AFR AF: 0.000795

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00320 Hom.: 2182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.53

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: rs948972; hg19: chr11-76894235;