Genetic Variant NKX3-1:c.*201T>C (chr8-23681020-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006167.4(NKX3-1):c.*201T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 476,546 control chromosomes in the GnomAD database, including 99,559 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29608 hom., cov: 32)

Exomes 𝑓: 0.65 ( 69951 hom. )

Consequence

NKX3-1
NM_006167.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Publications

15 publications found

Variant links:

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]

NKX3-1 links:

LOC107986930 (HGNC:):

LOC107986930 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NKX3-1	NM_006167.4	MANE Select	c.*201T>C	3_prime_UTR	Exon 2 of 2	NP_006158.2
NKX3-1	NM_001256339.1		c.*201T>C	3_prime_UTR	Exon 3 of 3	NP_001243268.1	Q99801-3
NKX3-1	NR_046072.2		n.158T>C	non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX3-1	ENST00000380871.5	TSL:1 MANE Select	c.*201T>C		3_prime_UTR	Exon 2 of 2	ENSP00000370253.4	Q99801-1
	NKX3-1	ENST00000523261.1	TSL:1	c.*201T>C		3_prime_UTR	Exon 3 of 3	ENSP00000429729.1	Q99801-3

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

94087

AN:

151994

Hom.:

29597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.634

GnomAD4 exome

AF:

0.653

AC:

211848

AN:

324434

Hom.:

69951

Cov.:

AF XY:

0.653

AC XY:

108221

AN XY:

165840

show subpopulations

African (AFR)

AF:

0.518

AC:

5694

AN:

10994

American (AMR)

AF:

0.631

AC:

8441

AN:

13374

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

7014

AN:

10952

East Asian (EAS)

AF:

0.659

AC:

18183

AN:

27606

South Asian (SAS)

AF:

0.596

AC:

9388

AN:

15742

European-Finnish (FIN)

AF:

0.557

AC:

12430

AN:

22302

Middle Eastern (MID)

AF:

0.627

AC:

953

AN:

1520

European-Non Finnish (NFE)

AF:

0.677

AC:

136647

AN:

201764

Other (OTH)

AF:

0.649

AC:

13098

AN:

20180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3365

6730

10095

13460

16825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.619

AC:

94141

AN:

152112

Hom.:

29608

Cov.:

AF XY:

0.613

AC XY:

45592

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.526

AC:

21821

AN:

41474

American (AMR)

AF:

0.624

AC:

9540

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2261

AN:

3470

East Asian (EAS)

AF:

0.708

AC:

3657

AN:

5162

South Asian (SAS)

AF:

0.606

AC:

2923

AN:

4820

European-Finnish (FIN)

AF:

0.545

AC:

5774

AN:

10592

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

46056

AN:

67986

Other (OTH)

AF:

0.630

AC:

1330

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1843

3687

5530

7374

9217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.657

Hom.:

52720

Bravo

AF:

0.623

Asia WGS

AF:

0.605

AC:

2104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

(source)

DANN

Benign

0.82

PhyloP100

-0.021

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over