chr12-57029733-C-T

Position:

• chr12-57029733-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_005379.4(MYO1A):​c.2724+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,614,204 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (4 hom.)
• Consequence: MYO1A NM_005379.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001580
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.713

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]

MYO1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-57029733-C-T is Benign according to our data. Variant chr12-57029733-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164581.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
• BS2: High AC in GnomAd4 at 376 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.2724+7G>A		splice_region_variant, intron_variant		ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.2724+7G>A		splice_region_variant, intron_variant			NP_001242970.1
MYO1A	XM_047428876.1	c.2724+7G>A		splice_region_variant, intron_variant			XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.2724+7G>A		splice_region_variant, intron_variant		1	NM_005379.4	ENSP00000300119.3
MYO1A	ENST00000442789.6	c.2724+7G>A		splice_region_variant, intron_variant		1		ENSP00000393392.2
MYO1A	ENST00000477864.1	n.287+7G>A		splice_region_variant, intron_variant		2
MYO1A	ENST00000554234.5	n.*169+7G>A		splice_region_variant, intron_variant		5		ENSP00000451033.1

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 376 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00140 AC: 351 AN: 251362 Hom.: 1 AF XY: 0.00115 AC XY: 156 AN XY: 135846

Gnomad AFR exome AF: 0.00461

Gnomad AMR exome AF: 0.00306

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000765

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.000837 AC: 1223 AN: 1461866 Hom.: 4 Cov.: 33 AF XY: 0.000810 AC XY: 589 AN XY: 727238

Gnomad4 AFR exome AF: 0.00526

Gnomad4 AMR exome AF: 0.00344

Gnomad4 ASJ exome AF: 0.00509

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000513

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00247 AC: 376 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74504

Gnomad4 AFR AF: 0.00570

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00150 Hom.: 1

Bravo AF: 0.00276

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.00101

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 18, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	MYO1A: BP4 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2017

2724+7G>A in Intron 25 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 0.5% (47/10406) of African chromosomes by the Ex ome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs559858 17). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
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: rs55985817; hg19: chr12-57423517;