12-57029413-T-C

Variant summary

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

The NM_005379.4(MYO1A):c.2877+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,613,792 control chromosomes in the GnomAD database, including 6,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (787 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5694 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-57029413-T-C is Benign according to our data. Variant chr12-57029413-T-C is described in ClinVar as [Benign]. Clinvar id is 1289007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1A	NM_005379.4	c.2877+22A>G		intron_variant		ENST00000300119.8
MYO1A	NM_001256041.2	c.2877+22A>G		intron_variant
MYO1A	XM_047428876.1	c.2877+22A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1A	ENST00000300119.8	c.2877+22A>G		intron_variant		1	NM_005379.4	P1
MYO1A	ENST00000442789.6	c.2877+22A>G		intron_variant		1		P1
MYO1A	ENST00000477864.1	n.462A>G		non_coding_transcript_exon_variant	4/4	2
MYO1A	ENST00000554234.5	c.*322+22A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14977 AN: 151930 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.0852

GnomAD3 exomes AF: 0.0974 AC: 24464 AN: 251208 Hom.: 1334 AF XY: 0.0967 AC XY: 13134 AN XY: 135774

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.0763

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.0993

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0842

Gnomad OTH exome AF: 0.0897

GnomAD4 exome AF: 0.0860 AC: 125770 AN: 1461744 Hom.: 5694 Cov.: 33 AF XY: 0.0858 AC XY: 62412 AN XY: 727178

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0921

Gnomad4 ASJ exome AF: 0.0742

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.0878

GnomAD4 genome AF: 0.0986 AC: 14999 AN: 152048 Hom.: 787 Cov.: 32 AF XY: 0.101 AC XY: 7530 AN XY: 74330

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0747

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0832 Hom.: 93

Bravo AF: 0.0989

Asia WGS AF: 0.139 AC: 480 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

Jun 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	13
Dann	Benign	0.72

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: rs56128678; hg19: chr12-57423197;