5-16877635-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 12 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 (MetaRNN=0.0014432967).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO10	NM_012334.3	MANE Select	c.94G>A	p.Val32Ile	missense	Exon 2 of 41	NP_036466.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO10	ENST00000513610.6	TSL:1 MANE Select	c.94G>A	p.Val32Ile	missense	Exon 2 of 41	ENSP00000421280.1
	MYO10	ENST00000507288.1	TSL:1	c.94G>A	p.Val32Ile	missense	Exon 2 of 4	ENSP00000426664.1
	MYO10	ENST00000274203.13	TSL:5	c.94G>A	p.Val32Ile	missense	Exon 2 of 41	ENSP00000274203.10

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

GnomAD2 exomes AF: 0.0324 AC: 8053 AN: 248852 AF XY: 0.0366

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 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

African (AFR) AF: 0.00233 AC: 78 AN: 33480

American (AMR) AF: 0.0109 AC: 489 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 1065 AN: 26126

East Asian (EAS) AF: 0.133 AC: 5261 AN: 39686

South Asian (SAS) AF: 0.124 AC: 10728 AN: 86176

European-Finnish (FIN) AF: 0.0115 AC: 613 AN: 53362

Middle Eastern (MID) AF: 0.0137 AC: 79 AN: 5768

European-Non Finnish (NFE) AF: 0.00678 AC: 7539 AN: 1111642

Other (OTH) AF: 0.0227 AC: 1372 AN: 60362

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

African (AFR) AF: 0.00296 AC: 123 AN: 41536

American (AMR) AF: 0.00680 AC: 104 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.120 AC: 617 AN: 5156

South Asian (SAS) AF: 0.135 AC: 649 AN: 4820

European-Finnish (FIN) AF: 0.00923 AC: 98 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 68030

Other (OTH) AF: 0.0185 AC: 39 AN: 2110

Alfa AF: 0.0122 Hom.: 201

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 v4.9

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
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Benign	0.54	T
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
Mutation Taster		=91/9	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: rs17707947; hg19: chr5-16877744; COSMIC: COSV72454523;