NM_001189.4:c.942G>C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001189.4(NKX3-2):ā€‹c.942G>Cā€‹(p.Pro314Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,606,442 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0041 ( 1 hom., cov: 33)
Exomes š‘“: 0.00076 ( 6 hom. )

Consequence

NKX3-2
NM_001189.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.00
Variant links:
Genes affected
NKX3-2 (HGNC:951): (NK3 homeobox 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; negative regulation of chondrocyte differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including animal organ development; embryonic skeletal system development; and intestinal epithelial cell development. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 4-13542053-C-G is Benign according to our data. Variant chr4-13542053-C-G is described in ClinVar as [Benign]. Clinvar id is 288013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NKX3-2NM_001189.4 linkc.942G>C p.Pro314Pro synonymous_variant Exon 2 of 2 ENST00000382438.6 NP_001180.1 P78367
NKX3-2XM_047416049.1 linkc.942G>C p.Pro314Pro synonymous_variant Exon 3 of 3 XP_047272005.1
NKX3-2XM_047416050.1 linkc.942G>C p.Pro314Pro synonymous_variant Exon 3 of 3 XP_047272006.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NKX3-2ENST00000382438.6 linkc.942G>C p.Pro314Pro synonymous_variant Exon 2 of 2 1 NM_001189.4 ENSP00000371875.5 P78367

Frequencies

GnomAD3 genomes
AF:
0.00400
AC:
608
AN:
152182
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0126
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00118
AC:
275
AN:
232338
Hom.:
1
AF XY:
0.000997
AC XY:
126
AN XY:
126408
show subpopulations
Gnomad AFR exome
AF:
0.0105
Gnomad AMR exome
AF:
0.00123
Gnomad ASJ exome
AF:
0.000310
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000515
Gnomad FIN exome
AF:
0.0000511
Gnomad NFE exome
AF:
0.000533
Gnomad OTH exome
AF:
0.00157
GnomAD4 exome
AF:
0.000757
AC:
1101
AN:
1454142
Hom.:
6
Cov.:
31
AF XY:
0.000735
AC XY:
531
AN XY:
722732
show subpopulations
Gnomad4 AFR exome
AF:
0.0117
Gnomad4 AMR exome
AF:
0.00128
Gnomad4 ASJ exome
AF:
0.000193
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000577
Gnomad4 FIN exome
AF:
0.000133
Gnomad4 NFE exome
AF:
0.000370
Gnomad4 OTH exome
AF:
0.00203
GnomAD4 genome
AF:
0.00405
AC:
617
AN:
152300
Hom.:
1
Cov.:
33
AF XY:
0.00380
AC XY:
283
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0128
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.000773
Hom.:
0
Bravo
AF:
0.00445
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
May 10, 2016
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
1.8
DANN
Benign
0.77

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.

Other links and lift over

dbSNP: rs111283169; hg19: chr4-13543677; API