chr4-13542008-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001189.4(NKX3-2):c.987C>T(p.Ala329Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000692 in 1,589,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00041 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
NKX3-2
NM_001189.4 synonymous
NM_001189.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.41
Genes affected
NKX3-2 (HGNC:951): (NK3 homeobox 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; negative regulation of chondrocyte differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including animal organ development; embryonic skeletal system development; and intestinal epithelial cell development. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 4-13542008-G-A is Benign according to our data. Variant chr4-13542008-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.41 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NKX3-2 | NM_001189.4 | c.987C>T | p.Ala329Ala | synonymous_variant | Exon 2 of 2 | ENST00000382438.6 | NP_001180.1 | |
NKX3-2 | XM_047416049.1 | c.987C>T | p.Ala329Ala | synonymous_variant | Exon 3 of 3 | XP_047272005.1 | ||
NKX3-2 | XM_047416050.1 | c.987C>T | p.Ala329Ala | synonymous_variant | Exon 3 of 3 | XP_047272006.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000407 AC: 62AN: 152250Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000968 AC: 20AN: 206676Hom.: 0 AF XY: 0.0000980 AC XY: 11AN XY: 112236
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GnomAD4 exome AF: 0.0000334 AC: 48AN: 1437518Hom.: 0 Cov.: 31 AF XY: 0.0000323 AC XY: 23AN XY: 713144
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GnomAD4 genome AF: 0.000407 AC: 62AN: 152368Hom.: 1 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74498
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Nov 06, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at