Variant rs4656579 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005149.3(TBX19):c.728-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,592,222 control chromosomes in the GnomAD database, including 357,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28832 hom., cov: 32)

Exomes 𝑓: 0.67 ( 329058 hom. )

Consequence

TBX19
NM_005149.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.642

Variant links:

Genes affected

TBX19 (HGNC:11596): (T-box transcription factor 19) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Mutations in this gene were found in patients with isolated deficiency of pituitary POMC-derived ACTH, suggesting an essential role for this gene in differentiation of the pituitary POMC lineage. ACTH deficiency is characterized by adrenal insufficiency symptoms such as weight loss, lack of appetite (anorexia), weakness, nausea, vomiting, and low blood pressure. [provided by RefSeq, Jul 2008]

TBX19 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-168304963-G-A is Benign according to our data. Variant chr1-168304963-G-A is described in ClinVar as [Benign]. Clinvar id is 1334932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX19	NM_005149.3 link	c.728-45G>A		intron_variant		ENST00000367821.8	NP_005140.1	O60806B3KRD9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TBX19	ENST00000367821.8 link	c.728-45G>A	intron_variant	1	NM_005149.3	ENSP00000356795.3	O60806
TBX19	ENST00000431969.5 link	c.524-3779G>A	intron_variant	5		ENSP00000397540.1	H0Y5A7
TBX19	ENST00000441464.1 link	c.224-45G>A	intron_variant	2		ENSP00000390731.1	H0Y4B1

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91957

AN:

151944

Hom.:

28810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.767

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.606

GnomAD3 exomes

AF:

0.603

AC:

148695

AN:

246620

Hom.:

46733

AF XY:

0.602

AC XY:

80637

AN XY:

133844

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.583

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.614

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.669

AC:

963900

AN:

1440160

Hom.:

329058

Cov.:

AF XY:

0.664

AC XY:

476576

AN XY:

717862

show subpopulations

Gnomad4 AFR exome

AF:

0.482

Gnomad4 AMR exome

AF:

0.583

Gnomad4 ASJ exome

AF:

0.663

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.448

Gnomad4 FIN exome

AF:

0.623

Gnomad4 NFE exome

AF:

0.711

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.605

AC:

92022

AN:

152062

Hom.:

28832

Cov.:

AF XY:

0.594

AC XY:

44118

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.487

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.652

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.424

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.681

Hom.:

53547

Bravo

AF:

0.601

Asia WGS

AF:

0.421

AC:

1465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital isolated adrenocorticotropic hormone deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.1

DANN

Benign

0.36

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