NM_012334.3:c.3991-65A>G

Variant names:

• chr5-16684000-T-C
• rs2303703
• NM_012334.3:c.3991-65A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYO10	NM_012334.3	c.3991-65A>G		intron_variant	Intron 29 of 40	ENST00000513610.6	NP_036466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6	c.3991-65A>G		intron_variant	Intron 29 of 40	1	NM_012334.3	ENSP00000421280.1
MYO10	ENST00000274203.13	c.4024-65A>G		intron_variant	Intron 29 of 40	5		ENSP00000274203.10
MYO10	ENST00000505695.5	c.2008-65A>G		intron_variant	Intron 11 of 22	2		ENSP00000421170.1
MYO10	ENST00000515803.5	c.2008-65A>G		intron_variant	Intron 11 of 22	2		ENSP00000425051.1

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

African (AFR) AF: 0.249 AC: 7374 AN: 29562

American (AMR) AF: 0.293 AC: 11596 AN: 39590

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7070 AN: 24524

East Asian (EAS) AF: 0.262 AC: 9800 AN: 37466

South Asian (SAS) AF: 0.379 AC: 29985 AN: 79220

European-Finnish (FIN) AF: 0.317 AC: 16301 AN: 51392

Middle Eastern (MID) AF: 0.242 AC: 1325 AN: 5478

European-Non Finnish (NFE) AF: 0.294 AC: 282148 AN: 958842

Other (OTH) AF: 0.302 AC: 16452 AN: 54422

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

African (AFR) AF: 0.260 AC: 10787 AN: 41492

American (AMR) AF: 0.264 AC: 4041 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5166

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3505 AN: 10570

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19323 AN: 67978

Other (OTH) AF: 0.271 AC: 573 AN: 2112

Alfa AF: 0.280 Hom.: 1280

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
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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