1-109296441-ATTTTT-A

Variant names:

• chr1-109296441-ATTTTT-A
• rs59806839
• NM_001010985.3:c.731-76_731-72delAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010985.3(MYBPHL):​c.731-76_731-72delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,252,262 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: not found (cov: 25)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.731-76_731-72delAAAAA		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.662-76_662-72delAAAAA		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.731-76_731-72delAAAAA		intron	N/A	ENSP00000349678.1	A2RUH7-1
	MYBPHL	ENST00000477962.1	TSL:1	n.150-1149_150-1145delAAAAA		intron	N/A
	MYBPHL	ENST00000968920.1		c.911-76_911-72delAAAAA		intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1252262 Hom.: 0 AF XY: 0.00000160 AC XY: 1 AN XY: 624256

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

African (AFR) AF: 0.00 AC: 0 AN: 27000

American (AMR) AF: 0.00 AC: 0 AN: 26640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21544

East Asian (EAS) AF: 0.00 AC: 0 AN: 35044

South Asian (SAS) AF: 0.00 AC: 0 AN: 71394

European-Finnish (FIN) AF: 0.0000265 AC: 1 AN: 37780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3774

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 976870

Other (OTH) AF: 0.00 AC: 0 AN: 52216

⚠️ 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 Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs59806839; hg19: chr1-109839063;