chr3-46858026-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000258.3(MYL3):​c.*89G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 640,720 control chromosomes in the GnomAD database, including 11,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3313 hom., cov: 31)
Exomes 𝑓: 0.15 ( 7714 hom. )

Consequence

MYL3
NM_000258.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
MYL3 (HGNC:7584): (myosin light chain 3) MYL3 encodes myosin light chain 3, an alkali light chain also referred to in the literature as both the ventricular isoform and the slow skeletal muscle isoform. Mutations in MYL3 have been identified as a cause of mid-left ventricular chamber type hypertrophic cardiomyopathy. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 3-46858026-C-T is Benign according to our data. Variant chr3-46858026-C-T is described in ClinVar as [Benign]. Clinvar id is 345568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46858026-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYL3NM_000258.3 linkuse as main transcriptc.*89G>A 3_prime_UTR_variant 7/7 ENST00000292327.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYL3ENST00000292327.6 linkuse as main transcriptc.*89G>A 3_prime_UTR_variant 7/71 NM_000258.3 P1

Frequencies

GnomAD3 genomes
AF:
0.183
AC:
27741
AN:
151872
Hom.:
3310
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.316
Gnomad AMI
AF:
0.197
Gnomad AMR
AF:
0.121
Gnomad ASJ
AF:
0.189
Gnomad EAS
AF:
0.224
Gnomad SAS
AF:
0.375
Gnomad FIN
AF:
0.133
Gnomad MID
AF:
0.231
Gnomad NFE
AF:
0.106
Gnomad OTH
AF:
0.176
GnomAD4 exome
AF:
0.152
AC:
74412
AN:
488730
Hom.:
7714
Cov.:
6
AF XY:
0.164
AC XY:
42339
AN XY:
258580
show subpopulations
Gnomad4 AFR exome
AF:
0.312
Gnomad4 AMR exome
AF:
0.106
Gnomad4 ASJ exome
AF:
0.185
Gnomad4 EAS exome
AF:
0.221
Gnomad4 SAS exome
AF:
0.370
Gnomad4 FIN exome
AF:
0.126
Gnomad4 NFE exome
AF:
0.105
Gnomad4 OTH exome
AF:
0.158
GnomAD4 genome
AF:
0.183
AC:
27780
AN:
151990
Hom.:
3313
Cov.:
31
AF XY:
0.187
AC XY:
13912
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.316
Gnomad4 AMR
AF:
0.121
Gnomad4 ASJ
AF:
0.189
Gnomad4 EAS
AF:
0.224
Gnomad4 SAS
AF:
0.375
Gnomad4 FIN
AF:
0.133
Gnomad4 NFE
AF:
0.106
Gnomad4 OTH
AF:
0.176
Alfa
AF:
0.124
Hom.:
2036
Bravo
AF:
0.182
Asia WGS
AF:
0.279
AC:
969
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy 8 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
9.4
DANN
Benign
0.73

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.

Other links and lift over

dbSNP: rs1042973; hg19: chr3-46899516; COSMIC: COSV52767732; COSMIC: COSV52767732; API