8-23680495-C-T

Variant names:

• chr8-23680495-C-T
• rs4872176
• NM_006167.4:c.*726G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006167.4(NKX3-1):​c.*726G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,070 control chromosomes in the GnomAD database, including 16,820 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 0.45 (16817 hom., cov: 32)
  • Exomes 𝑓: 0.41 (3 hom.)
• Consequence: NKX3-1 NM_006167.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 13 publications found

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]

LOC107986930 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX3-1	ENST00000380871.5	c.*726G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_006167.4	ENSP00000370253.4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68786 AN: 151920 Hom.: 16814 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.406 AC: 13 AN: 32 Hom.: 3 Cov.: 0 AF XY: 0.458 AC XY: 11 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 12 AN: 30

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.453 AC: 68801 AN: 152038 Hom.: 16817 Cov.: 32 AF XY: 0.453 AC XY: 33690 AN XY: 74318

African (AFR) AF: 0.266 AC: 11008 AN: 41458

American (AMR) AF: 0.493 AC: 7522 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1946 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3640 AN: 5162

South Asian (SAS) AF: 0.550 AC: 2651 AN: 4822

European-Finnish (FIN) AF: 0.453 AC: 4787 AN: 10570

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35701 AN: 67970

Other (OTH) AF: 0.460 AC: 972 AN: 2112

Alfa AF: 0.401 Hom.: 2163

Bravo AF: 0.455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.41
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4872176; hg19: chr8-23538008;