Variant chr5-173232508-C-A 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_004387.4(NKX2-5):c.*61G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,589,370 control chromosomes in the GnomAD database, including 96,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7485 hom., cov: 33)

Exomes 𝑓: 0.35 ( 89051 hom. )

Consequence

NKX2-5
NM_004387.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.816

Variant links:

Genes affected

NKX2-5 (HGNC:2488): (NK2 homeobox 5) This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

NKX2-5 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=-0.85).

BP6

Variant 5-173232508-C-A is Benign according to our data. Variant chr5-173232508-C-A is described in ClinVar as [Benign]. Clinvar id is 211668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-173232508-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NKX2-5	NM_004387.4 linkuse as main transcript	c.*61G>T	3_prime_UTR_variant	2/2	ENST00000329198.5
NKX2-5	NM_001166175.2 linkuse as main transcript	c.*989G>T	3_prime_UTR_variant	2/2
NKX2-5	NM_001166176.2 linkuse as main transcript	c.*835G>T	3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-5	ENST00000329198.5 linkuse as main transcript	c.*61G>T		3_prime_UTR_variant	2/2	1	NM_004387.4	P1	P52952-1

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46560

AN:

152124

Hom.:

7474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.0584

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.303

GnomAD4 exome

AF:

0.348

AC:

500047

AN:

1437128

Hom.:

89051

Cov.:

AF XY:

0.350

AC XY:

250238

AN XY:

714484

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.242

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.0748

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.306

AC:

46597

AN:

152242

Hom.:

7485

Cov.:

AF XY:

0.300

AC XY:

22323

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.260

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.0583

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.341

Hom.:

11982

Bravo

AF:

0.300

Asia WGS

AF:

0.240

AC:

839

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.6

DANN

Benign

0.72

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