NM_006167.4:c.220_222delGACinsAAT

Variant names:

• chr8-23682668-GTC-ATT
• NM_006167.4:c.220_222delGACinsAAT
• NKX3-1 p.Asp74Asn

Variant summary

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

The NM_006167.4(NKX3-1):​c.220_222delGACinsAAT​(p.Asp74Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D74H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NKX3-1 NM_006167.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• 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.

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.220_222delGACinsAAT	p.Asp74Asn	missense	N/A	NP_006158.2
	NKX3-1	NM_001256339.1		c.34-39_34-37delGACinsAAT		intron	N/A	NP_001243268.1	Q99801-3
	NKX3-1	NR_046072.2		n.35+234_35+236delGACinsAAT		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.220_222delGACinsAAT	p.Asp74Asn	missense	N/A	ENSP00000370253.4	Q99801-1
	NKX3-1	ENST00000523261.1	TSL:1	c.34-39_34-37delGACinsAAT		intron	N/A	ENSP00000429729.1	Q99801-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-23540181;