8-23681262-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006167.4(NKX3-1):āc.664T>Cā(p.Tyr222His) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
NKX3-1
NM_006167.4 missense
NM_006167.4 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 5.93
Genes affected
NKX3-1 (HGNC:7838): (NK3 homeobox 1) This gene encodes a homeobox-containing transcription factor. This transcription factor functions as a negative regulator of epithelial cell growth in prostate tissue. Aberrant expression of this gene is associated with prostate tumor progression. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41450378).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKX3-1 | NM_006167.4 | c.664T>C | p.Tyr222His | missense_variant | 2/2 | ENST00000380871.5 | |
LOC107986930 | XR_001745842.2 | n.1312+12512A>G | intron_variant, non_coding_transcript_variant | ||||
NKX3-1 | NM_001256339.1 | c.439T>C | p.Tyr147His | missense_variant | 3/3 | ||
NKX3-1 | NR_046072.2 | n.36-120T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKX3-1 | ENST00000380871.5 | c.664T>C | p.Tyr222His | missense_variant | 2/2 | 1 | NM_006167.4 | P2 | |
NKX3-1 | ENST00000523261.1 | c.439T>C | p.Tyr147His | missense_variant | 3/3 | 1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455478Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722604
GnomAD4 exome
AF:
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1
AN:
1455478
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Cov.:
31
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AC XY:
1
AN XY:
722604
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Jun 24, 2022 | The c.664T>C (p.Y222H) alteration is located in exon 2 (coding exon 2) of the NKX3-1 gene. This alteration results from a T to C substitution at nucleotide position 664, causing the tyrosine (Y) at amino acid position 222 to be replaced by a histidine (H). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of glycosylation at P221 (P = 0.1191);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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
Publications
No publications associated with this variant yet.