rs768775204
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001136271.3(NKX2-6):c.276G>A(p.Gln92=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,539,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001136271.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-6 | NM_001136271.3 | c.276G>A | p.Gln92= | splice_region_variant, synonymous_variant | 2/2 | ENST00000325017.4 | |
LOC107986930 | XR_001745842.2 | n.1312+34331C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-6 | ENST00000325017.4 | c.276G>A | p.Gln92= | splice_region_variant, synonymous_variant | 2/2 | 2 | NM_001136271.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000145 AC: 20AN: 137850Hom.: 0 AF XY: 0.000146 AC XY: 11AN XY: 75124
GnomAD4 exome AF: 0.000130 AC: 181AN: 1387192Hom.: 0 Cov.: 33 AF XY: 0.000139 AC XY: 95AN XY: 684618
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74384
ClinVar
Submissions by phenotype
Conotruncal heart malformations Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 27, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
NKX2-6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 28, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at