rs1012659513

Variant names:

• chr8-23681581-C-A
• rs1012659513
• NM_006167.4:c.345G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-23681581-C-A
• chr8-23681581-C-G
• chr8-23681581-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006167.4(NKX3-1):​c.345G>T​(p.Arg115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: NKX3-1 NM_006167.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039796174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX3-1	NM_006167.4	c.345G>T	p.Arg115Ser	missense_variant	Exon 2 of 2	ENST00000380871.5	NP_006158.2
NKX3-1	NM_001256339.1	c.120G>T	p.Arg40Ser	missense_variant	Exon 3 of 3		NP_001243268.1
NKX3-1	NR_046072.2	n.36-439G>T		intron_variant	Intron 1 of 1
LOC107986930	XR_001745842.2	n.1312+12831C>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX3-1	ENST00000380871.5	c.345G>T	p.Arg115Ser	missense_variant	Exon 2 of 2	1	NM_006167.4	ENSP00000370253.4
NKX3-1	ENST00000523261.1	c.120G>T	p.Arg40Ser	missense_variant	Exon 3 of 3	1		ENSP00000429729.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727086

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.68
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	-0.75	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.75	N;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.0	B;.
Vest4		0.018
MutPred		0.25		Loss of MoRF binding (P = 0.0359);.;
MVP		0.85
MPC		0.23
ClinPred		0.026	T
GERP RS		4.4
Varity_R		0.070
gMVP		0.31

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: rs1012659513; hg19: chr8-23539094;