rs114876057

Variant names:

• chr12-57038792-C-T
• rs114876057
• NM_005379.4:c.1533+17G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005379.4(MYO1A):​c.1533+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 1,614,102 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (1 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0450
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-57038792-C-T is Benign according to our data. Variant chr12-57038792-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 531 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.1533+17G>A		intron_variant	Intron 16 of 27	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.1533+17G>A		intron_variant	Intron 17 of 28		NP_001242970.1
MYO1A	XM_047428876.1	c.1533+17G>A		intron_variant	Intron 17 of 28		XP_047284832.1
MYO1A	XM_011538373.3	c.1533+17G>A		intron_variant	Intron 16 of 24		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.1533+17G>A		intron_variant	Intron 16 of 27	1	NM_005379.4	ENSP00000300119.3
MYO1A	ENST00000442789.6	c.1533+17G>A		intron_variant	Intron 17 of 28	1		ENSP00000393392.2
MYO1A	ENST00000476795.1	n.430+17G>A		intron_variant	Intron 2 of 2	5
MYO1A	ENST00000554234.5	n.1047+17G>A		intron_variant	Intron 12 of 23	5		ENSP00000451033.1

Frequencies

GnomAD3 genomes AF: 0.00347 AC: 528 AN: 152184 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

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: 0.0000441

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000889 AC: 223 AN: 250804 AF XY: 0.000612

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000326 AC: 476 AN: 1461800 Hom.: 1 Cov.: 32 AF XY: 0.000296 AC XY: 215 AN XY: 727200

African (AFR) AF: 0.0116 AC: 388 AN: 33480

American (AMR) AF: 0.000559 AC: 25 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111972

Other (OTH) AF: 0.000646 AC: 39 AN: 60384

GnomAD4 genome AF: 0.00349 AC: 531 AN: 152302 Hom.: 3 Cov.: 32 AF XY: 0.00352 AC XY: 262 AN XY: 74476

African (AFR) AF: 0.0118 AC: 492 AN: 41568

American (AMR) AF: 0.00189 AC: 29 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00381

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 17, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114876057; hg19: chr12-57432576;