Variant 5-173233371-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000329198.5(NKX2-5):c.335-162G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NKX2-5
ENST00000329198.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11092529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NKX2-5	NM_004387.4 linkuse as main transcript	c.335-162G>C		intron_variant		ENST00000329198.5	NP_004378.1
NKX2-5	NM_001166176.2 linkuse as main transcript	c.428G>C	p.Arg143Pro	missense_variant	2/2		NP_001159648.1
NKX2-5	NM_001166175.2 linkuse as main transcript	c.*126G>C		3_prime_UTR_variant	2/2		NP_001159647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-5	ENST00000424406.2 linkuse as main transcript	c.*126G>C		3_prime_UTR_variant	2/2	1		ENSP00000395378		P52952-3
NKX2-5	ENST00000329198.5 linkuse as main transcript	c.335-162G>C		intron_variant		1	NM_004387.4	ENSP00000327758	P1	P52952-1
NKX2-5	ENST00000521848.1 linkuse as main transcript	c.428G>C	p.Arg143Pro	missense_variant	2/2	2		ENSP00000427906		P52952-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000717

AC:

AN:

139470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1384804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000191

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.2

DANN

Benign

0.72

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.40

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.55

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Vest4

0.34

MutPred

0.30

Gain of loop (P = 0.0045);

MVP

0.42

ClinPred

0.075

GERP RS

-2.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over