Variant chr10-99535094-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_145285.3(NKX2-3):c.468G>A(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,609,354 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 18 hom. )

Consequence

NKX2-3
NM_145285.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.44

Variant links:

Genes affected

NKX2-3 (HGNC:7836): (NK2 homeobox 3) This gene encodes a homeodomain-containing transcription factor. The encoded protein is a member of the NKX family of homeodomain transcription factors. Studies of similar proteins in mouse and rat have indicated a potential role in cellular differentiation.[provided by RefSeq, Mar 2010]

NKX2-3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 10-99535094-G-A is Benign according to our data. Variant chr10-99535094-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640746.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

BS2

High AC in GnomAd4 at 565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKX2-3	NM_145285.3 link	c.468G>A	p.Ser156Ser	synonymous_variant	2/2	ENST00000344586.9	NP_660328.2	Q8TAU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-3	ENST00000344586.9 link	c.468G>A	p.Ser156Ser	synonymous_variant	2/2	2	NM_145285.3	ENSP00000342828.7		Q8TAU0

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

565

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00614

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00386

AC:

918

AN:

237608

Hom.:

AF XY:

0.00383

AC XY:

497

AN XY:

129660

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00215

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00417

Gnomad NFE exome

AF:

0.00637

Gnomad OTH exome

AF:

0.00292

GnomAD4 exome

AF:

0.00464

AC:

6755

AN:

1457000

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

3294

AN XY:

724342

show subpopulations

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.00212

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00351

Gnomad4 NFE exome

AF:

0.00544

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.00371

AC:

565

AN:

152354

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00614

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00337

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

NKX2-3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.9

DANN

Benign

0.96

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