1-109296441-ATTTTT-ATT

Variant names:

• chr1-109296441-ATTT-A
• rs59806839
• NM_001010985.3:c.731-74_731-72delAAA

Variant summary

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

The NM_001010985.3(MYBPHL):​c.731-74_731-72delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,246,930 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 0.0 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYBPHL NM_001010985.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• Publications: 0 publications found

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

ACMG classification

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.731-74_731-72delAAA		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.662-74_662-72delAAA		intron	N/A	NP_001252542.1	A2RUH7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPHL	ENST00000357155.2	TSL:1 MANE Select	c.731-74_731-72delAAA		intron	N/A	ENSP00000349678.1	A2RUH7-1
	MYBPHL	ENST00000477962.1	TSL:1	n.150-1147_150-1145delAAA		intron	N/A
	MYBPHL	ENST00000968920.1		c.911-74_911-72delAAA		intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141462 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000745 AC: 929 AN: 1246930 Hom.: 0 AF XY: 0.000759 AC XY: 472 AN XY: 621614

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

African (AFR) AF: 0.00119 AC: 32 AN: 26856

American (AMR) AF: 0.000868 AC: 23 AN: 26486

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 24 AN: 21438

East Asian (EAS) AF: 0.000948 AC: 33 AN: 34792

South Asian (SAS) AF: 0.000802 AC: 57 AN: 71096

European-Finnish (FIN) AF: 0.00125 AC: 47 AN: 37634

Middle Eastern (MID) AF: 0.000797 AC: 3 AN: 3764

European-Non Finnish (NFE) AF: 0.000674 AC: 656 AN: 972862

Other (OTH) AF: 0.00104 AC: 54 AN: 52002

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 141462 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 68414

African (AFR) AF: 0.00 AC: 0 AN: 38446

American (AMR) AF: 0.00 AC: 0 AN: 14052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3308

East Asian (EAS) AF: 0.00 AC: 0 AN: 4842

South Asian (SAS) AF: 0.00 AC: 0 AN: 4436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64536

Other (OTH) AF: 0.00 AC: 0 AN: 1924

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs59806839; hg19: chr1-109839063;