rs2303703

Positions:

• chr5-16684000-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012334.3(MYO10):​c.3991-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,432,588 control chromosomes in the GnomAD database, including 63,851 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6080 hom., cov: 32)
  • Exomes 𝑓: 0.30 (57771 hom.)
• Consequence: MYO10 NM_012334.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.69

Genes affected

MYO10 (HGNC:7593): (myosin X) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-10 (MYH10). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. This gene functions as an actin-based molecular motor and plays a role in integration of F-actin and microtubule cytoskeletons during meiosis. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO10	NM_012334.3	c.3991-65A>G		intron_variant		ENST00000513610.6	NP_036466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6	c.3991-65A>G		intron_variant		1	NM_012334.3	ENSP00000421280	P1
MYO10	ENST00000274203.13	c.4024-65A>G		intron_variant		5		ENSP00000274203
MYO10	ENST00000505695.5	c.2008-65A>G		intron_variant		2		ENSP00000421170
MYO10	ENST00000515803.5	c.2008-65A>G		intron_variant		2		ENSP00000425051

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42644 AN: 151972 Hom.: 6069 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.298 AC: 382051 AN: 1280496 Hom.: 57771 AF XY: 0.300 AC XY: 192981 AN XY: 642760

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.281 AC: 42677 AN: 152092 Hom.: 6080 Cov.: 32 AF XY: 0.282 AC XY: 20956 AN XY: 74342

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.271

Alfa AF: 0.281 Hom.: 1258

Bravo AF: 0.276

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0070
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2303703; hg19: chr5-16684109; COSMIC: COSV57023381;