Variant 7-101622097-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138403.5(MYL10):c.453G>C(p.Lys151Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,613,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

MYL10
NM_138403.5 missense, splice_region

Scores

Splicing: ADA: 0.00002439

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

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:

Genome browser will be placed here

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=0.07968086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL10	NM_138403.5 linkuse as main transcript	c.453G>C	p.Lys151Asn	missense_variant, splice_region_variant	5/8	ENST00000223167.5	NP_612412.2	Q9BUA6
MYL10	XM_017012793.2 linkuse as main transcript	c.216G>C	p.Lys72Asn	missense_variant, splice_region_variant	4/7		XP_016868282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYL10	ENST00000223167.5 linkuse as main transcript	c.453G>C	p.Lys151Asn	missense_variant, splice_region_variant	5/8	1	NM_138403.5	ENSP00000223167.4	Q9BUA6
MYL10	ENST00000642629.2 linkuse as main transcript	c.276G>C	p.Lys92Asn	missense_variant, splice_region_variant	4/7			ENSP00000493793.2	A0A2R8YDI2
MYL10	ENST00000706943.1 linkuse as main transcript	c.216G>C	p.Lys72Asn	missense_variant, splice_region_variant	4/7			ENSP00000516663.1	A0A9L9PXJ4

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000212

AC:

AN:

250338

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

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:

0.000408

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000372

AC:

544

AN:

1460976

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

258

AN XY:

726840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000467

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000256

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000357

Hom.:

Bravo

AF:

0.000287

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000772

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

Sep 20, 2024

The c.453G>C (p.K151N) alteration is located in exon 5 (coding exon 5) of the MYL10 gene. This alteration results from a G to C substitution at nucleotide position 453, causing the lysine (K) at amino acid position 151 to be replaced by an asparagine (N). 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

0.89

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.064

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.080

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.23

N;.

REVEL

Uncertain

0.29

Sift

Benign

0.72

T;.

Sift4G

Benign

0.75

T;.

Polyphen

0.98

D;.

Vest4

0.77

MutPred

0.40

Loss of ubiquitination at K151 (P = 0.0103);.;

MVP

0.80

MPC

0.49

ClinPred

0.075

GERP RS

0.22

Varity_R

0.12

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over