10-99535368-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_145285.3(NKX2-3):c.742G>A(p.Ala248Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,454,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_145285.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-3 | NM_145285.3 | c.742G>A | p.Ala248Thr | missense_variant | 2/2 | ENST00000344586.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-3 | ENST00000344586.9 | c.742G>A | p.Ala248Thr | missense_variant | 2/2 | 2 | NM_145285.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151482Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000997 AC: 13AN: 1303380Hom.: 0 Cov.: 34 AF XY: 0.0000156 AC XY: 10AN XY: 641974
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151482Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 73980
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2024 | The c.742G>A (p.A248T) alteration is located in exon 2 (coding exon 2) of the NKX2-3 gene. This alteration results from a G to A substitution at nucleotide position 742, causing the alanine (A) at amino acid position 248 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at