5-173235023-C-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004387.4(NKX2-5):c.61G>C(p.Glu21Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000587 in 1,612,066 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E21E) has been classified as Benign.
Frequency
Consequence
NM_004387.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | ENST00000329198.5 | |
NKX2-5 | NM_001166176.2 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | ||
NKX2-5 | NM_001166175.2 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | ||
NKX2-5 | XM_017009071.3 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | 1 | NM_004387.4 | P1 | |
NKX2-5 | ENST00000424406.2 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | 1 | |||
NKX2-5 | ENST00000521848.1 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | 2 | |||
NKX2-5 | ENST00000517440.1 | c.61G>C | p.Glu21Gln | missense_variant | 1/2 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000703 AC: 107AN: 152180Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00110 AC: 267AN: 242910Hom.: 3 AF XY: 0.000977 AC XY: 130AN XY: 133046
GnomAD4 exome AF: 0.000575 AC: 839AN: 1459768Hom.: 7 Cov.: 33 AF XY: 0.000610 AC XY: 443AN XY: 726232
GnomAD4 genome ? AF: 0.000703 AC: 107AN: 152298Hom.: 0 Cov.: 30 AF XY: 0.000765 AC XY: 57AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | NKX2-5: PP3, BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 31, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | This variant is associated with the following publications: (PMID: 11714651, 17891434, 20725931, 16930004, 25274754, 25524324, 24782644, 12798584, 25333069, 25713730, 15810002, 21165553, 21110066, 20456451, 18375573, 17544441, 26805889, 27152669, 20497191, 20462343, 25944381, 14607454, 31256874, 28549997) - |
Atrial septal defect 7 Benign:2
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Tetralogy of Fallot Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Nov 20, 2001 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital heart disease Benign:1
Likely benign, no assertion criteria provided | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 02, 2015 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2017 | 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