rs4872176

Positions:

• chr8-23680495-C-A
• chr8-23680495-C-G
• chr8-23680495-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006167.4(NKX3-1):​c.*726G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 152,132 control chromosomes in the GnomAD database, including 25 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 0.013 (25 hom., cov: 32)
  • Exomes 𝑓: 0.031 (0 hom.)
• Consequence: NKX3-1 NM_006167.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKX3-1	NM_006167.4	c.*726G>T		3_prime_UTR_variant	2/2	ENST00000380871.5	NP_006158.2
NKX3-1	NM_001256339.1	c.*726G>T		3_prime_UTR_variant	3/3		NP_001243268.1
NKX3-1	NR_046072.2	n.683G>T		non_coding_transcript_exon_variant	2/2
LOC107986930	XR_001745842.2	n.1312+11745C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX3-1	ENST00000380871.5	c.*726G>T		3_prime_UTR_variant	2/2	1	NM_006167.4	ENSP00000370253.4

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1909 AN: 151982 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00334

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0313 AC: 1 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 24

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0333

GnomAD4 genome AF: 0.0125 AC: 1908 AN: 152100 Hom.: 25 Cov.: 32 AF XY: 0.0129 AC XY: 961 AN XY: 74354

Gnomad4 AFR AF: 0.00333

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00315 Hom.: 2135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs4872176; hg19: chr8-23538008;