rs1036449900

Variant names:

• chr8-23682721-C-G
• rs1036449900
• NM_006167.4:c.169G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006167.4(NKX3-1):​c.169G>C​(p.Glu57Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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)
• Consequence: NKX3-1 NM_006167.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12767899).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX3-1	NM_006167.4	MANE Select	c.169G>C	p.Glu57Gln	missense	Exon 1 of 2	NP_006158.2
	NKX3-1	NM_001256339.1		c.34-90G>C		intron	N/A	NP_001243268.1	Q99801-3
	NKX3-1	NR_046072.2		n.35+183G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX3-1	ENST00000380871.5	TSL:1 MANE Select	c.169G>C	p.Glu57Gln	missense	Exon 1 of 2	ENSP00000370253.4	Q99801-1
	NKX3-1	ENST00000523261.1	TSL:1	c.34-90G>C		intron	N/A	ENSP00000429729.1	Q99801-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.15
Sift	Benign	0.29	T
Sift4G	Benign	0.52	T
Polyphen		0.072	B
Vest4		0.13
MutPred		0.15		Loss of glycosylation at P56 (P = 0.0526)
MVP		0.83
MPC		0.23
ClinPred		0.12	T
GERP RS		2.5
PromoterAI		0.014	Neutral
Varity_R		0.062
gMVP		0.24
Mutation Taster		=97/3	polymorphism

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: rs1036449900; hg19: chr8-23540234;