12-57029038-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005379.4(MYO1A):c.3005+94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000976 in 1,609,206 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00059 (10 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.325

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic 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 autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-57029038-G-A is Benign according to our data. Variant chr12-57029038-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 708 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1A	NM_005379.4	c.3005+94C>T		intron_variant		ENST00000300119.8
MYO1A	NM_001256041.2	c.3005+94C>T		intron_variant
MYO1A	XM_047428876.1	c.3005+94C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1A	ENST00000300119.8	c.3005+94C>T		intron_variant		1	NM_005379.4	P1
MYO1A	ENST00000442789.6	c.3005+94C>T		intron_variant		1		P1
MYO1A	ENST00000554234.5	c.*450+94C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 708 AN: 151954 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000592 AC: 863 AN: 1457134 Hom.: 10 Cov.: 30 AF XY: 0.000527 AC XY: 382 AN XY: 725212

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.00466 AC: 708 AN: 152072 Hom.: 6 Cov.: 31 AF XY: 0.00441 AC XY: 328 AN XY: 74330

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00423 Hom.: 0

Bravo AF: 0.00523

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.6
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs115363422; hg19: chr12-57422822;