Variant 8-23681395-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_006167.4(NKX3-1):c.531T>C(p.Tyr177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,614,174 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 77 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 62 hom. )

Consequence

NKX3-1
NM_006167.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13

Variant links:

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]

NKX3-1 links:

LOC107986930 (HGNC:):

LOC107986930 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 8-23681395-A-G is Benign according to our data. Variant chr8-23681395-A-G is described in ClinVar as [Benign]. Clinvar id is 709245.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NKX3-1	NM_006167.4 linkuse as main transcript	c.531T>C	p.Tyr177=	synonymous_variant	2/2	ENST00000380871.5
LOC107986930	XR_001745842.2 linkuse as main transcript	n.1312+12645A>G		intron_variant, non_coding_transcript_variant
NKX3-1	NM_001256339.1 linkuse as main transcript	c.306T>C	p.Tyr102=	synonymous_variant	3/3
NKX3-1	NR_046072.2 linkuse as main transcript	n.36-253T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX3-1	ENST00000380871.5 linkuse as main transcript	c.531T>C	p.Tyr177=	synonymous_variant	2/2	1	NM_006167.4	P2	Q99801-1
NKX3-1	ENST00000523261.1 linkuse as main transcript	c.306T>C	p.Tyr102=	synonymous_variant	3/3	1		A2	Q99801-3

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2677

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00451

AC:

1133

AN:

251492

Hom.:

AF XY:

0.00335

AC XY:

455

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0629

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00168

AC:

2459

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1068

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0614

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00386

GnomAD4 genome

AF:

0.0176

AC:

2682

AN:

152280

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1268

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0603

Gnomad4 AMR

AF:

0.00934

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00953

Hom.:

Bravo

AF:

0.0204

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.7

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over