Variant 7-101623011-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138403.5(MYL10):c.335C>G(p.Thr112Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,613,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

MYL10
NM_138403.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

MYL10 (HGNC:29825): (myosin light chain 10) Predicted to enable calcium ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MYL10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013761044).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL10	NM_138403.5 linkuse as main transcript	c.335C>G	p.Thr112Ser	missense_variant	4/8	ENST00000223167.5	NP_612412.2	Q9BUA6
MYL10	XM_017012793.2 linkuse as main transcript	c.98C>G	p.Thr33Ser	missense_variant	3/7		XP_016868282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYL10	ENST00000223167.5 linkuse as main transcript	c.335C>G	p.Thr112Ser	missense_variant	4/8	1	NM_138403.5	ENSP00000223167.4	Q9BUA6
MYL10	ENST00000642629.2 linkuse as main transcript	c.158C>G	p.Thr53Ser	missense_variant	3/7			ENSP00000493793.2	A0A2R8YDI2
MYL10	ENST00000706943.1 linkuse as main transcript	c.98C>G	p.Thr33Ser	missense_variant	3/7			ENSP00000516663.1	A0A9L9PXJ4

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000490

AC:

123

AN:

251202

Hom.:

AF XY:

0.000596

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000329

AC:

481

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

277

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000302

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000784

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.335C>G (p.T112S) alteration is located in exon 4 (coding exon 4) of the MYL10 gene. This alteration results from a C to G substitution at nucleotide position 335, causing the threonine (T) at amino acid position 112 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.36

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

3.3

M;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

D;.

REVEL

Uncertain

0.39

Sift

Benign

0.033

D;.

Sift4G

Uncertain

0.023

D;.

Polyphen

0.11

B;.

Vest4

0.76

MutPred

0.44

Gain of relative solvent accessibility (P = 0.0522);.;

MVP

0.67

MPC

0.29

ClinPred

0.13

GERP RS

4.0

Varity_R

0.19

gMVP

0.61

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over