6-133274782-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PVS1_SupportingBS2
The NM_004100.5(EYA4):āc.2T>Cā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000744 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_004100.5 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251230Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135782
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461428Hom.: 0 Cov.: 29 AF XY: 0.00000825 AC XY: 6AN XY: 727046
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:1
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Dilated cardiomyopathy 1J Uncertain:1
This sequence change affects the initiator methionine of the EYA4 mRNA. The next in-frame methionine is located at codon 30. This variant is present in population databases (rs200593099, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with EYA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 191657). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Cardiovascular phenotype Uncertain:1
The p.M1? variant (also known as c.2T>C) is located in coding exon 1 of the EYA4 gene and results from a T to C substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). Variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame; however, there is an in-frame methionine 29 amino acids from the initiation site, which may result in N-terminal truncation of unknown functional significance. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at