dbSNP rs35675040: NKX3-1:p.Pro198Pro (chr8-23681332-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006167.4(NKX3-1):c.594G>C(p.Pro198Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,614,056 control chromosomes in the GnomAD database, including 1 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. Synonymous variant affecting the same amino acid position (i.e. P198P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 1 hom. )

Consequence

NKX3-1
NM_006167.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

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 made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX3-1	NM_006167.4 link	c.594G>C	p.Pro198Pro	synonymous_variant	Exon 2 of 2	ENST00000380871.5	NP_006158.2	Q99801-1
NKX3-1	NM_001256339.1 link	c.369G>C	p.Pro123Pro	synonymous_variant	Exon 3 of 3		NP_001243268.1	Q99801-3
NKX3-1	NR_046072.2 link	n.36-190G>C		intron_variant	Intron 1 of 1
LOC107986930	XR_001745842.2 link	n.1312+12582C>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX3-1	ENST00000380871.5 link	c.594G>C	p.Pro198Pro	synonymous_variant	Exon 2 of 2	1	NM_006167.4	ENSP00000370253.4		Q99801-1
NKX3-1	ENST00000523261.1 link	c.369G>C	p.Pro123Pro	synonymous_variant	Exon 3 of 3	1		ENSP00000429729.1		Q99801-3

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251460

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000394

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000671

Hom.:

Bravo

AF:

0.000476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.053

DANN

Benign

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over