chr8-23682779-G-T

Position:

• chr8-23682779-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006167.4(NKX3-1):​c.111C>A​(p.Asp37Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NKX3-1 NM_006167.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25250515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX3-1	NM_006167.4	c.111C>A	p.Asp37Glu	missense_variant	1/2	ENST00000380871.5
LOC107986930	XR_001745842.2	n.1312+14029G>T		intron_variant, non_coding_transcript_variant
NKX3-1	NM_001256339.1	c.33+78C>A		intron_variant
NKX3-1	NR_046072.2	n.35+125C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX3-1	ENST00000380871.5	c.111C>A	p.Asp37Glu	missense_variant	1/2	1	NM_006167.4	P2
NKX3-1	ENST00000523261.1	c.33+78C>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420304 Hom.: 0 Cov.: 31 AF XY: 0.00000283 AC XY: 2 AN XY: 705706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.26
Sift	Benign	0.23	T
Sift4G	Benign	0.80	T
Polyphen		0.91	P
Vest4		0.093
MutPred		0.16		Gain of MoRF binding (P = 0.116);
MVP		0.96
MPC		0.20
ClinPred		0.70	D
GERP RS		3.5
Varity_R		0.10
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-23540292;