14-23389064-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002471.4(MYH6):c.3979-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00068 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MYH6
NM_002471.4 intron

Scores

Splicing: ADA: 0.002634

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.427

Publications

1 publications found

Variant links:

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

MYH6 Gene-Disease associations (from GenCC):

MYH-6 related congenital heart defects
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 14
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Keppen-Lubinsky syndrome
Inheritance: AD Classification: MODERATE Submitted by: Illumina
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atrial septal defect 3
Inheritance: AD Classification: LIMITED Submitted by: G2P
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 14-23389064-G-T is Benign according to our data. Variant chr14-23389064-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000679 (46/67780) while in subpopulation EAS AF = 0.00648 (27/4164). AF 95% confidence interval is 0.00458. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002471.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH6	NM_002471.4	MANE Select	c.3979-9C>A		intron	N/A	NP_002462.2	P13533

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH6	ENST00000405093.9	TSL:5 MANE Select	c.3979-9C>A	intron	N/A	ENSP00000386041.3	P13533
MYH6	ENST00000968262.1		c.4012-9C>A	intron	N/A	ENSP00000638321.1
MYH6	ENST00000968257.1		c.3979-9C>A	intron	N/A	ENSP00000638316.1

Frequencies

GnomAD3 genomes

AF:

0.000679

AC:

AN:

67766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000566

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00646

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.000305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000550

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00129

AC:

124

AN:

96074

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.000705

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000675

AC:

774

AN:

1146168

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

360

AN XY:

569898

show subpopulations

African (AFR)

AF:

0.000251

AC:

AN:

23918

American (AMR)

AF:

0.000209

AC:

AN:

38212

Ashkenazi Jewish (ASJ)

AF:

0.000446

AC:

AN:

17944

East Asian (EAS)

AF:

0.00457

AC:

176

AN:

38530

South Asian (SAS)

AF:

0.000472

AC:

AN:

72080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39018

Middle Eastern (MID)

AF:

0.000430

AC:

AN:

4648

European-Non Finnish (NFE)

AF:

0.000554

AC:

479

AN:

864698

Other (OTH)

AF:

0.00129

AC:

AN:

47120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000679

AC:

AN:

67780

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

AN XY:

33670

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

6222

American (AMR)

AF:

0.000565

AC:

AN:

8850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1592

East Asian (EAS)

AF:

0.00648

AC:

AN:

4164

South Asian (SAS)

AF:

0.00115

AC:

AN:

2602

European-Finnish (FIN)

AF:

0.000305

AC:

AN:

6554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.0000550

AC:

AN:

36332

Other (OTH)

AF:

0.00

AC:

AN:

920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000287

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Cardiomyopathy (1)

Hypertrophic cardiomyopathy 14 (1)

MYH6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.0

(source)

DANN

Benign

0.92

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0026

dbscSNV1_RF

Benign

0.12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over