1-236686671-G-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001103.4(ACTN2):c.-3G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000894 in 1,555,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001103.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.-3G>T | 5_prime_UTR_variant | Exon 1 of 21 | ENST00000366578.6 | NP_001094.1 | ||
ACTN2 | NM_001278343.2 | c.-3G>T | 5_prime_UTR_variant | Exon 1 of 21 | NP_001265272.1 | |||
ACTN2 | NR_184402.1 | n.173G>T | non_coding_transcript_exon_variant | Exon 1 of 23 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000857 AC: 13AN: 151688Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000170 AC: 36AN: 212092Hom.: 0 AF XY: 0.000198 AC XY: 23AN XY: 116442
GnomAD4 exome AF: 0.0000898 AC: 126AN: 1403548Hom.: 0 Cov.: 31 AF XY: 0.0000888 AC XY: 62AN XY: 698366
GnomAD4 genome AF: 0.0000857 AC: 13AN: 151688Hom.: 0 Cov.: 31 AF XY: 0.0000945 AC XY: 7AN XY: 74080
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.-3G>T variant in ACTN2 has been previously identified by our laboratory in 2 Ashkenazi Jewish adults with HCM. It has also been identified in 10/64028 Eur opean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs201920417). This variant is located in the 5' UTR and is pa rt of the translation initiation (Kozak) sequence, but its effect on translation is unknown. In summary, the clinical significance of the c.-3G>T variant is unc ertain. -
Hypertrophic cardiomyopathy Uncertain:1
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Cardiomyopathy Benign:1
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not provided Benign:1
See Variant Classification Assertion Criteria. -
Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at