dbSNP rs11781886: NKX3-1:c.-15G>A (chr8-23682904-C-T) – 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.-15G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,430,684 control chromosomes in the GnomAD database, including 396,762 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 0.72 ( 39199 hom., cov: 32)

Exomes 𝑓: 0.75 ( 357563 hom. )

Consequence

NKX3-1
NM_006167.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

31 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=-0.73).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 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.-15G>A	5_prime_UTR	Exon 1 of 2	NP_006158.2
NKX3-1	NR_046072.2		n.35G>A	splice_region non_coding_transcript_exon	Exon 1 of 2
NKX3-1	NM_001256339.1		c.-15G>A	upstream_gene	N/A	NP_001243268.1	Q99801-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX3-1	ENST00000380871.5	TSL:1 MANE Select	c.-15G>A		5_prime_UTR	Exon 1 of 2	ENSP00000370253.4	Q99801-1
	NKX3-1	ENST00000523261.1	TSL:1	c.-15G>A		upstream_gene	N/A	ENSP00000429729.1	Q99801-3

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

108811

AN:

151756

Hom.:

39174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.809

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.725

GnomAD2 exomes

AF:

0.720

AC:

34082

AN:

47312

AF XY:

0.724

show subpopulations

Gnomad AFR exome

AF:

0.724

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.768

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.747

AC:

955240

AN:

1278818

Hom.:

357563

Cov.:

AF XY:

0.746

AC XY:

465788

AN XY:

624684

show subpopulations

African (AFR)

AF:

0.690

AC:

17712

AN:

25664

American (AMR)

AF:

0.682

AC:

15512

AN:

22730

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

14102

AN:

19600

East Asian (EAS)

AF:

0.662

AC:

19152

AN:

28922

South Asian (SAS)

AF:

0.675

AC:

43273

AN:

64062

European-Finnish (FIN)

AF:

0.645

AC:

19879

AN:

30810

Middle Eastern (MID)

AF:

0.733

AC:

2764

AN:

3772

European-Non Finnish (NFE)

AF:

0.760

AC:

783359

AN:

1030206

Other (OTH)

AF:

0.744

AC:

39487

AN:

53052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

14026

28052

42077

56103

70129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19722

39444

59166

78888

98610

<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:

0.717

AC:

108888

AN:

151866

Hom.:

39199

Cov.:

AF XY:

0.709

AC XY:

52610

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.698

AC:

28931

AN:

41442

American (AMR)

AF:

0.691

AC:

10566

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2496

AN:

3470

East Asian (EAS)

AF:

0.715

AC:

3643

AN:

5094

South Asian (SAS)

AF:

0.673

AC:

3247

AN:

4824

European-Finnish (FIN)

AF:

0.620

AC:

6553

AN:

10570

Middle Eastern (MID)

AF:

0.801

AC:

234

AN:

292

European-Non Finnish (NFE)

AF:

0.753

AC:

51100

AN:

67864

Other (OTH)

AF:

0.722

AC:

1524

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1529

3058

4588

6117

7646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.740

Hom.:

38624

Bravo

AF:

0.724

Asia WGS

AF:

0.670

AC:

2322

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.3

(source)

DANN

Benign

0.90

PhyloP100

-1.8

PromoterAI

-0.31

Neutral

(source)

Mutation Taster

=300/0

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