rs144770764

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001189.4(NKX3-2):​c.987C>T​(p.Ala329Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000692 in 1,589,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00041 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

NKX3-2
NM_001189.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.41
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 -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 4-13542008-G-A is Benign according to our data. Variant chr4-13542008-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.41 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NKX3-2NM_001189.4 linkc.987C>T p.Ala329Ala synonymous_variant Exon 2 of 2 ENST00000382438.6 NP_001180.1 P78367
NKX3-2XM_047416049.1 linkc.987C>T p.Ala329Ala synonymous_variant Exon 3 of 3 XP_047272005.1
NKX3-2XM_047416050.1 linkc.987C>T p.Ala329Ala 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.987C>T p.Ala329Ala synonymous_variant Exon 2 of 2 1 NM_001189.4 ENSP00000371875.5 P78367

Frequencies

GnomAD3 genomes
AF:
0.000407
AC:
62
AN:
152250
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00147
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000968
AC:
20
AN:
206676
Hom.:
0
AF XY:
0.0000980
AC XY:
11
AN XY:
112236
show subpopulations
Gnomad AFR exome
AF:
0.00152
Gnomad AMR exome
AF:
0.0000326
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000111
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000334
AC:
48
AN:
1437518
Hom.:
0
Cov.:
31
AF XY:
0.0000323
AC XY:
23
AN XY:
713144
show subpopulations
Gnomad4 AFR exome
AF:
0.00128
Gnomad4 AMR exome
AF:
0.0000484
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:
9.08e-7
Gnomad4 OTH exome
AF:
0.0000506
GnomAD4 genome
AF:
0.000407
AC:
62
AN:
152368
Hom.:
1
Cov.:
32
AF XY:
0.000376
AC XY:
28
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.00147
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000251
Hom.:
0
Bravo
AF:
0.000453

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Nov 06, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
6.3
DANN
Benign
0.94

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: rs144770764; hg19: chr4-13543632; COSMIC: COSV101220044; COSMIC: COSV101220044; API