chr5-173232683-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_004387.4(NKX2-5):c.861C>T(p.Ala287Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,611,166 control chromosomes in the GnomAD database, including 18 homozygotes. 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_004387.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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NKX2-5 | NM_004387.4 | c.861C>T | p.Ala287Ala | synonymous_variant | Exon 2 of 2 | ENST00000329198.5 | NP_004378.1 | |
NKX2-5 | NM_001166176.2 | c.*660C>T | 3_prime_UTR_variant | Exon 2 of 2 | NP_001159648.1 | |||
NKX2-5 | NM_001166175.2 | c.*814C>T | 3_prime_UTR_variant | Exon 2 of 2 | NP_001159647.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00638 AC: 971AN: 152274Hom.: 8 Cov.: 32
GnomAD3 exomes AF: 0.00175 AC: 433AN: 247808Hom.: 4 AF XY: 0.00133 AC XY: 179AN XY: 134948
GnomAD4 exome AF: 0.000763 AC: 1113AN: 1458774Hom.: 10 Cov.: 34 AF XY: 0.000706 AC XY: 512AN XY: 725200
GnomAD4 genome AF: 0.00640 AC: 975AN: 152392Hom.: 8 Cov.: 32 AF XY: 0.00594 AC XY: 443AN XY: 74526
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:4
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Atrial septal defect 7 Benign:1
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not provided Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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