rs703752
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004387.4(NKX2-5):c.*61G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,589,370 control chromosomes in the GnomAD database, including 96,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.31 ( 7485 hom., cov: 33)
Exomes 𝑓: 0.35 ( 89051 hom. )
Consequence
NKX2-5
NM_004387.4 3_prime_UTR
NM_004387.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.816
Genes affected
NKX2-5 (HGNC:2488): (NK2 homeobox 5) This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 5-173232508-C-A is Benign according to our data. Variant chr5-173232508-C-A is described in ClinVar as [Benign]. Clinvar id is 211668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-173232508-C-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.*61G>T | 3_prime_UTR_variant | 2/2 | ENST00000329198.5 | ||
NKX2-5 | NM_001166175.2 | c.*989G>T | 3_prime_UTR_variant | 2/2 | |||
NKX2-5 | NM_001166176.2 | c.*835G>T | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.*61G>T | 3_prime_UTR_variant | 2/2 | 1 | NM_004387.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.306 AC: 46560AN: 152124Hom.: 7474 Cov.: 33
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GnomAD4 exome AF: 0.348 AC: 500047AN: 1437128Hom.: 89051 Cov.: 42 AF XY: 0.350 AC XY: 250238AN XY: 714484
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GnomAD4 genome ? AF: 0.306 AC: 46597AN: 152242Hom.: 7485 Cov.: 33 AF XY: 0.300 AC XY: 22323AN XY: 74422
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 15, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at