NM_005379.4:c.1185T>C

Variant names:

• chr12-57041268-A-G
• rs17546153
• NM_005379.4:c.1185T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005379.4(MYO1A):​c.1185T>C​(p.Phe395Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,914 control chromosomes in the GnomAD database, including 1,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (89 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1226 hom.)
• Consequence: MYO1A NM_005379.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.49
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-57041268-A-G is Benign according to our data. Variant chr12-57041268-A-G is described in ClinVar as Benign. ClinVar VariationId is 45306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.49 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1A	NM_005379.4	MANE Select	c.1185T>C	p.Phe395Phe	synonymous	Exon 14 of 28	NP_005370.1	Q9UBC5
	MYO1A	NM_001256041.2		c.1185T>C	p.Phe395Phe	synonymous	Exon 15 of 29	NP_001242970.1	Q9UBC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1A	ENST00000300119.8	TSL:1 MANE Select	c.1185T>C	p.Phe395Phe	synonymous	Exon 14 of 28	ENSP00000300119.3	Q9UBC5
	MYO1A	ENST00000442789.6	TSL:1	c.1185T>C	p.Phe395Phe	synonymous	Exon 15 of 29	ENSP00000393392.2	Q9UBC5
	MYO1A	ENST00000907120.1		c.1317T>C	p.Phe439Phe	synonymous	Exon 14 of 28	ENSP00000577179.1

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4517 AN: 152164 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00640

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0344

GnomAD2 exomes AF: 0.0356 AC: 8947 AN: 251328 AF XY: 0.0374

Gnomad AFR exome AF: 0.00541

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0336

Gnomad NFE exome AF: 0.0441

Gnomad OTH exome AF: 0.0509

GnomAD4 exome AF: 0.0372 AC: 54366 AN: 1461632 Hom.: 1226 Cov.: 31 AF XY: 0.0373 AC XY: 27142 AN XY: 727120

African (AFR) AF: 0.00621 AC: 208 AN: 33474

American (AMR) AF: 0.0227 AC: 1016 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2863 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0285 AC: 2459 AN: 86250

European-Finnish (FIN) AF: 0.0340 AC: 1814 AN: 53414

Middle Eastern (MID) AF: 0.0791 AC: 454 AN: 5738

European-Non Finnish (NFE) AF: 0.0387 AC: 43079 AN: 1111820

Other (OTH) AF: 0.0409 AC: 2468 AN: 60378

GnomAD4 genome AF: 0.0296 AC: 4513 AN: 152282 Hom.: 89 Cov.: 32 AF XY: 0.0291 AC XY: 2167 AN XY: 74458

African (AFR) AF: 0.00635 AC: 264 AN: 41544

American (AMR) AF: 0.0268 AC: 410 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0229 AC: 110 AN: 4812

European-Finnish (FIN) AF: 0.0359 AC: 381 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2838 AN: 68030

Other (OTH) AF: 0.0345 AC: 73 AN: 2116

Alfa AF: 0.0406 Hom.: 132

Bravo AF: 0.0281

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.0518

EpiControl AF: 0.0513

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.3
DANN	Benign	0.60
PhyloP100		2.5
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17546153; hg19: chr12-57435052; COSMIC: COSV108098385; COSMIC: COSV108098385;