12-57028944-A-T

Position:

• chr12-57028944-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005379.4(MYO1A):​c.3006-63T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,600,898 control chromosomes in the GnomAD database, including 1,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (276 hom., cov: 31)
  • Exomes 𝑓: 0.028 (777 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.411

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-57028944-A-T is Benign according to our data. Variant chr12-57028944-A-T is described in ClinVar as [Benign]. Clinvar id is 1257585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.3006-63T>A		intron_variant		ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.3006-63T>A		intron_variant			NP_001242970.1
MYO1A	XM_047428876.1	c.3006-63T>A		intron_variant			XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.3006-63T>A		intron_variant		1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6	c.3006-63T>A		intron_variant		1		ENSP00000393392	P1
MYO1A	ENST00000554234.5	c.*451-63T>A		intron_variant, NMD_transcript_variant		5		ENSP00000451033

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7478 AN: 151514 Hom.: 274 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0745

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0284 AC: 41098 AN: 1449266 Hom.: 777 Cov.: 31 AF XY: 0.0280 AC XY: 20124 AN XY: 719574

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0700

Gnomad4 EAS exome AF: 0.0000761

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.0397

Gnomad4 NFE exome AF: 0.0268

Gnomad4 OTH exome AF: 0.0314

GnomAD4 genome AF: 0.0494 AC: 7488 AN: 151632 Hom.: 276 Cov.: 31 AF XY: 0.0480 AC XY: 3555 AN XY: 74100

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0745

Gnomad4 EAS AF: 0.000973

Gnomad4 SAS AF: 0.0105

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0432 Hom.: 22

Bravo AF: 0.0513

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.73

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: rs56347319; hg19: chr12-57422728;