chr10-99533462-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_145285.3(NKX2-3):c.331C>A(p.Pro111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000827 in 1,584,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000084 ( 1 hom. )
Consequence
NKX2-3
NM_145285.3 missense
NM_145285.3 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -1.48
Genes affected
NKX2-3 (HGNC:7836): (NK2 homeobox 3) This gene encodes a homeodomain-containing transcription factor. The encoded protein is a member of the NKX family of homeodomain transcription factors. Studies of similar proteins in mouse and rat have indicated a potential role in cellular differentiation.[provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012977153).
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX2-3 | NM_145285.3 | c.331C>A | p.Pro111Thr | missense_variant | 1/2 | ENST00000344586.9 | |
NKX2-3 | XM_011539370.2 | c.331C>A | p.Pro111Thr | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX2-3 | ENST00000344586.9 | c.331C>A | p.Pro111Thr | missense_variant | 1/2 | 2 | NM_145285.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152204Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000126 AC: 25AN: 198556Hom.: 0 AF XY: 0.000206 AC XY: 22AN XY: 106726
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GnomAD4 exome AF: 0.0000845 AC: 121AN: 1432630Hom.: 1 Cov.: 34 AF XY: 0.000120 AC XY: 85AN XY: 709166
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74360
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3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.331C>A (p.P111T) alteration is located in exon 1 (coding exon 1) of the NKX2-3 gene. This alteration results from a C to A substitution at nucleotide position 331, causing the proline (P) at amino acid position 111 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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