Genetic Variant MYBPHL:c.731-73_731-72dupAA (chr1-109296441-A-ATT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001010985.3(MYBPHL):c.731-73_731-72dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,390,388 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0016 ( 0 hom. )

Consequence

MYBPHL
NM_001010985.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.471

Publications

0 publications found

Variant links:

Genes affected

MYBPHL (HGNC:30434): (myosin binding protein H like) This gene encodes a protein with two immunoglobulin superfamily domains and a fibronectin 3 domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

MYBPHL Gene-Disease associations (from GenCC):

familial dilated cardiomyopathy
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

MYBPHL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010985.3. 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
	MYBPHL	NM_001010985.3	MANE Select	c.731-73_731-72dupAA		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.662-73_662-72dupAA		intron	N/A	NP_001252542.1	A2RUH7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYBPHL	ENST00000357155.2	TSL:1 MANE Select	c.731-72_731-71insAA	intron	N/A	ENSP00000349678.1	A2RUH7-1
MYBPHL	ENST00000477962.1	TSL:1	n.150-1145_150-1144insAA	intron	N/A
MYBPHL	ENST00000968920.1		c.911-72_911-71insAA	intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes

AF:

0.000615

AC:

AN:

141480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000142

Gnomad ASJ

AF:

0.000302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000229

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000480

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00165

AC:

2056

AN:

1248870

Hom.:

AF XY:

0.00165

AC XY:

1025

AN XY:

622698

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00260

AC:

AN:

26924

American (AMR)

AF:

0.000601

AC:

AN:

26608

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

21500

East Asian (EAS)

AF:

0.000400

AC:

AN:

34974

South Asian (SAS)

AF:

0.00107

AC:

AN:

71284

European-Finnish (FIN)

AF:

0.000875

AC:

AN:

37720

Middle Eastern (MID)

AF:

0.000797

AC:

AN:

3766

European-Non Finnish (NFE)

AF:

0.00177

AC:

1725

AN:

974036

Other (OTH)

AF:

0.00169

AC:

AN:

52058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.279

Heterozygous variant carriers

191

382

572

763

954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

136

204

272

340

<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:

0.000615

AC:

AN:

141518

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

AN XY:

68480

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

38530

American (AMR)

AF:

0.000142

AC:

AN:

14066

Ashkenazi Jewish (ASJ)

AF:

0.000302

AC:

AN:

3308

East Asian (EAS)

AF:

0.00

AC:

AN:

4830

South Asian (SAS)

AF:

0.00

AC:

AN:

4408

European-Finnish (FIN)

AF:

0.000229

AC:

AN:

8736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000480

AC:

AN:

64536

Other (OTH)

AF:

0.00

AC:

AN:

1936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000397

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-109296441-ATTTTT-ATTTTTTT

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