NM_012334.3:c.94G>A

Variant names:

• chr5-16877635-C-T
• rs17707947
• NM_012334.3:c.94G>A

Variant summary

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

The NM_012334.3(MYO10):​c.94G>A​(p.Val32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,613,532 control chromosomes in the GnomAD database, including 1,413 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (90 hom., cov: 32)
  • Exomes 𝑓: 0.019 (1323 hom.)
• Consequence: MYO10 NM_012334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 (MetaRNN=0.0014432967).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO10	NM_012334.3	c.94G>A	p.Val32Ile	missense_variant	Exon 2 of 41	ENST00000513610.6	NP_036466.2
MYO10	XM_006714475.4	c.94G>A	p.Val32Ile	missense_variant	Exon 2 of 40		XP_006714538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6	c.94G>A	p.Val32Ile	missense_variant	Exon 2 of 41	1	NM_012334.3	ENSP00000421280.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2215 AN: 152112 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.00923

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00654

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.0324 AC: 8053 AN: 248852 Hom.: 443 AF XY: 0.0366 AC XY: 4943 AN XY: 135004

Gnomad AFR exome AF: 0.00323

Gnomad AMR exome AF: 0.0122

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.103

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.00858

Gnomad OTH exome AF: 0.0265

GnomAD4 exome AF: 0.0186 AC: 27224 AN: 1461304 Hom.: 1323 Cov.: 31 AF XY: 0.0218 AC XY: 15880 AN XY: 726956

Gnomad4 AFR exome AF: 0.00233

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0115

Gnomad4 NFE exome AF: 0.00678

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0146 AC: 2220 AN: 152228 Hom.: 90 Cov.: 32 AF XY: 0.0167 AC XY: 1245 AN XY: 74430

Gnomad4 AFR AF: 0.00296

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.00923

Gnomad4 NFE AF: 0.00653

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0117 Hom.: 79

Bravo AF: 0.0115

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00422 AC: 17

ESP6500EA AF: 0.00671 AC: 56

ExAC AF: 0.0337 AC: 4071

Asia WGS AF: 0.122 AC: 422 AN: 3478

EpiCase AF: 0.00802

EpiControl AF: 0.00830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.011	T;T;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.74	T;T;T;T
MetaRNN	Benign	0.0014	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	.;L;.;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.11	T;T;T;T
Sift4G	Benign	0.54	T;T;.;D
Polyphen		0.010	.;B;.;.
Vest4		0.055
MPC		0.14
ClinPred		0.0051	T
GERP RS		3.5
Varity_R		0.023
gMVP		0.25

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: rs17707947; hg19: chr5-16877744; COSMIC: COSV72454523;