rs141658242

Positions:

• chr12-57048275-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005379.4(MYO1A):​c.49G>C​(p.Glu17Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000598 in 1,614,164 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: MYO1A NM_005379.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.52

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012277007).
• BP6: Variant 12-57048275-C-G is Benign according to our data. Variant chr12-57048275-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 45312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 475 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.49G>C	p.Glu17Gln	missense_variant	2/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.49G>C	p.Glu17Gln	missense_variant	3/29		NP_001242970.1
MYO1A	XM_047428876.1	c.49G>C	p.Glu17Gln	missense_variant	3/29		XP_047284832.1
MYO1A	XM_011538373.3	c.49G>C	p.Glu17Gln	missense_variant	2/25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.49G>C	p.Glu17Gln	missense_variant	2/28	1	NM_005379.4	ENSP00000300119.3

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 471 AN: 152186 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.000738 AC: 185 AN: 250828 Hom.: 0 AF XY: 0.000546 AC XY: 74 AN XY: 135516

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.000376

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: 0.0000265

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000336 AC: 491 AN: 1461860 Hom.: 1 Cov.: 32 AF XY: 0.000300 AC XY: 218 AN XY: 727236

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.000811

GnomAD4 genome AF: 0.00312 AC: 475 AN: 152304 Hom.: 4 Cov.: 32 AF XY: 0.00287 AC XY: 214 AN XY: 74466

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.00367

ESP6500AA AF: 0.0118 AC: 52

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000955 AC: 116

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

Glu17Gln in Exon 02 of MYO1A: This variant is not expected to have clinical sign ificance because it has been identified in 1.3% (48/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs141658242). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;D;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	.;D;D
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	N;N;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0060	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.39
MVP		0.92
MPC		0.45
ClinPred		0.0061	T
GERP RS		4.8
Varity_R		0.49
gMVP		0.47

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: rs141658242; hg19: chr12-57442059;