NM_012334.3:c.2169+445T>C

Variant names:

• chr5-16710463-A-G
• rs2288440
• NM_012334.3:c.2169+445T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012334.3(MYO10):​c.2169+445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,010 control chromosomes in the GnomAD database, including 9,729 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 0.35 (9729 hom., cov: 32)
• Consequence: MYO10 NM_012334.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.26
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO10	NM_012334.3	c.2169+445T>C		intron_variant	Intron 21 of 40	ENST00000513610.6	NP_036466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6	c.2169+445T>C		intron_variant	Intron 21 of 40	1	NM_012334.3	ENSP00000421280.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52784 AN: 151892 Hom.: 9723 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52842 AN: 152010 Hom.: 9729 Cov.: 32 AF XY: 0.349 AC XY: 25939 AN XY: 74306

African (AFR) AF: 0.449 AC: 18594 AN: 41454

American (AMR) AF: 0.321 AC: 4897 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2353 AN: 5158

South Asian (SAS) AF: 0.343 AC: 1653 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3501 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19749 AN: 67970

Other (OTH) AF: 0.323 AC: 680 AN: 2108

Alfa AF: 0.307 Hom.: 3847

Bravo AF: 0.352

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.21
PhyloP100		-5.3
Mutation Taster		=100/0	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: rs2288440; hg19: chr5-16710572;