rs150907076

chr12-57046851-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.541+12C>T variant causes a intron change. The variant allele was found at a frequency of 0.000387 in 1,613,588 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.09

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=-0.7).
• BP6: Variant 12-57046851-G-A is Benign according to our data. Variant chr12-57046851-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 164598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1A	NM_005379.4	c.541+12C>T		intron_variant		ENST00000300119.8
MYO1A	NM_001256041.2	c.541+12C>T		intron_variant
MYO1A	XM_011538373.3	c.541+12C>T		intron_variant
MYO1A	XM_047428876.1	c.541+12C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1A	ENST00000300119.8	c.541+12C>T		intron_variant		1	NM_005379.4	P1
MYO1A	ENST00000442789.6	c.541+12C>T		intron_variant		1		P1
MYO1A	ENST00000492945.5	c.-21+3036C>T		intron_variant		4
MYO1A	ENST00000554234.5	c.55+12C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 283 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00643

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000398 AC: 100 AN: 251392 Hom.: 0 AF XY: 0.000272 AC XY: 37 AN XY: 135850

Gnomad AFR exome AF: 0.00584

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000233 AC: 341 AN: 1461388 Hom.: 2 Cov.: 32 AF XY: 0.000208 AC XY: 151 AN XY: 727036

Gnomad4 AFR exome AF: 0.00921

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.000348

GnomAD4 genome AF: 0.00187 AC: 284 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74404

Gnomad4 AFR AF: 0.00643

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00124 Hom.: 0

Bravo AF: 0.00211

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

541+12C>T in Intron 07 of MYO1A: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 0.4% (16/3738) of African American chromosomes f rom a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wash ington.edu/EVS; dbSNP rs150907076). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	15
Dann	Benign	0.62

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: rs150907076; hg19: chr12-57440635;