Genetic Variant MYO1A:c.1333-8C>G (chr12-57039017-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005379.4(MYO1A):c.1333-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MYO1A
NM_005379.4 splice_region, intron

Scores

Splicing: ADA: 0.0005158

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYO1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4 link	c.1333-8C>G	splice_region_variant, intron_variant	Intron 15 of 27	ENST00000300119.8	NP_005370.1	Q9UBC5
MYO1A	NM_001256041.2 link	c.1333-8C>G	splice_region_variant, intron_variant	Intron 16 of 28		NP_001242970.1	Q9UBC5B2R643
MYO1A	XM_047428876.1 link	c.1333-8C>G	splice_region_variant, intron_variant	Intron 16 of 28		XP_047284832.1
MYO1A	XM_011538373.3 link	c.1333-8C>G	splice_region_variant, intron_variant	Intron 15 of 24		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO1A	ENST00000300119.8 link	c.1333-8C>G	splice_region_variant, intron_variant	Intron 15 of 27	1	NM_005379.4	ENSP00000300119.3	Q9UBC5
MYO1A	ENST00000442789.6 link	c.1333-8C>G	splice_region_variant, intron_variant	Intron 16 of 28	1		ENSP00000393392.2	Q9UBC5
MYO1A	ENST00000476795.1 link	n.230-8C>G	splice_region_variant, intron_variant	Intron 1 of 2	5
MYO1A	ENST00000554234.5 link	n.847-8C>G	splice_region_variant, intron_variant	Intron 11 of 23	5		ENSP00000451033.1	G3V342

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459200

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

85906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110662

Other (OTH)

AF:

0.0000498

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.54

PhyloP100

-1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.096

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over