rs767243751
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004387.4(NKX2-5):c.300C>G(p.Pro100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P100P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
NKX2-5
NM_004387.4 synonymous
NM_004387.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.323
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 5-173234784-G-C is Benign according to our data. Variant chr5-173234784-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2971019.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.323 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-5 | NM_004387.4 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | ENST00000329198.5 | |
NKX2-5 | NM_001166176.2 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | ||
NKX2-5 | NM_001166175.2 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | ||
NKX2-5 | XM_017009071.3 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-5 | ENST00000329198.5 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | 1 | NM_004387.4 | P1 | |
NKX2-5 | ENST00000424406.2 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | 1 | |||
NKX2-5 | ENST00000521848.1 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | 2 | |||
NKX2-5 | ENST00000517440.1 | c.300C>G | p.Pro100= | synonymous_variant | 1/2 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrial septal defect 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at