dbSNP rs189877968: MYO10:p.Arg2049Leu (chr5-16666723-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012334.3(MYO10):c.6146G>T(p.Arg2049Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,606,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2049H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

MYO10
NM_012334.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.72

Variant links:

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]

MYO10 links:

RETREG1-AS1 (HGNC:55551): (RETREG1 antisense RNA 1)

RETREG1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23022056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO10	NM_012334.3 link	c.6146G>T	p.Arg2049Leu	missense_variant	Exon 41 of 41	ENST00000513610.6	NP_036466.2	Q9HD67-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO10	ENST00000513610.6 link	c.6146G>T	p.Arg2049Leu	missense_variant	Exon 41 of 41	1	NM_012334.3	ENSP00000421280.1		Q9HD67-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000845

AC:

AN:

236548

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1454242

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

722904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;T;T

Eigen

Benign

-0.061

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D;.;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.4

.;L;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

.;N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0090

.;D;D;D

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.47

.;P;.;.

Vest4

0.37

MutPred

0.34

.;Gain of sheet (P = 0.0266);.;.;

MVP

0.81

MPC

0.22

ClinPred

0.58

GERP RS

5.5

Varity_R

0.18

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over