rs257048

Positions:

• chr5-16694258-G-A
• chr5-16694258-G-C

Variant summary

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

The NM_012334.3(MYO10):​c.3800+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,501,132 control chromosomes in the GnomAD database, including 1,190 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 0.054 (637 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (553 hom.)
• Consequence: MYO10 NM_012334.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.977

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO10	NM_012334.3	c.3800+113C>T		intron_variant		ENST00000513610.6	NP_036466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6	c.3800+113C>T		intron_variant		1	NM_012334.3	ENSP00000421280	P1
MYO10	ENST00000274203.13	c.3833+113C>T		intron_variant		5		ENSP00000274203
MYO10	ENST00000505695.5	c.1817+113C>T		intron_variant		2		ENSP00000421170
MYO10	ENST00000515803.5	c.1817+113C>T		intron_variant		2		ENSP00000425051

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8176 AN: 152180 Hom.: 635 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00607

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.00906 AC: 12219 AN: 1348834 Hom.: 553 AF XY: 0.00838 AC XY: 5591 AN XY: 667480

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0142

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.00134

Gnomad4 FIN exome AF: 0.000875

Gnomad4 NFE exome AF: 0.00447

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.0539 AC: 8203 AN: 152298 Hom.: 637 Cov.: 33 AF XY: 0.0518 AC XY: 3856 AN XY: 74466

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00607

Gnomad4 OTH AF: 0.0411

Alfa AF: 0.0130 Hom.: 30

Bravo AF: 0.0614

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.68

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: rs257048; hg19: chr5-16694367;