12-57029304-C-T

Position:

• chr12-57029304-C-T

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.2878-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,613,508 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 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (16 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.457

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=-0.78).
• BP6: Variant 12-57029304-C-T is Benign according to our data. Variant chr12-57029304-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 352 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.2878-45G>A		intron_variant		ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.2878-45G>A		intron_variant			NP_001242970.1
MYO1A	XM_047428876.1	c.2878-45G>A		intron_variant			XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.2878-45G>A		intron_variant		1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6	c.2878-45G>A		intron_variant		1		ENSP00000393392	P1
MYO1A	ENST00000554234.5	c.*323-45G>A		intron_variant, NMD_transcript_variant		5		ENSP00000451033

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00215 AC: 537 AN: 249508 Hom.: 2 AF XY: 0.00218 AC XY: 295 AN XY: 135274

Gnomad AFR exome AF: 0.000255

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.0000473

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00284 AC: 4152 AN: 1461308 Hom.: 16 Cov.: 33 AF XY: 0.00273 AC XY: 1984 AN XY: 726972

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00463

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.0000378

Gnomad4 NFE exome AF: 0.00330

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74394

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00343

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00325 Hom.: 0

Bravo AF: 0.00271

Asia WGS AF: 0.000577 AC: 2 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

May 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.49

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: rs202207957; hg19: chr12-57423088;