dbSNP rs6587239: GATA5:p.Lys284Asn (chr20-62465895-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080473.5(GATA5):c.852G>T(p.Lys284Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. K284K) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GATA5
NM_080473.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0710

Publications

0 publications found

Variant links:

Genes affected

GATA5 (HGNC:15802): (GATA binding protein 5) The protein encoded by this gene is a transcription factor that contains two GATA-type zinc fingers. The encoded protein is known to bind to hepatocyte nuclear factor-1alpha (HNF-1alpha), and this interaction is essential for cooperative activation of the intestinal lactase-phlorizin hydrolase promoter. In other organisms, similar proteins may be involved in the establishment of cardiac smooth muscle cell diversity. [provided by RefSeq, Jul 2008]

GATA5 Gene-Disease associations (from GenCC):

familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial bicuspid aortic valve
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tetralogy of fallot
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital heart defects, multiple types, 5
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

GATA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA5	NM_080473.5 link	c.852G>T	p.Lys284Asn	missense_variant	Exon 5 of 7	ENST00000252997.3	NP_536721.1	Q9BWX5
GATA5	XM_006723699.3 link	c.852G>T	p.Lys284Asn	missense_variant	Exon 5 of 7		XP_006723762.1	Q9BWX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA5	ENST00000252997.3 link	c.852G>T	p.Lys284Asn	missense_variant	Exon 5 of 7	1	NM_080473.5	ENSP00000252997.2		Q9BWX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443550

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33202

American (AMR)

AF:

0.00

AC:

AN:

42272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39004

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103154

Other (OTH)

AF:

0.00

AC:

AN:

59654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.93

MetaRNN

Pathogenic

0.87

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.1

PhyloP100

-0.071

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-4.9

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.65

MutPred

0.32

Loss of methylation at K284 (P = 0.0025);

MVP

1.0

MPC

0.49

ClinPred

0.99

GERP RS

1.9

Varity_R

0.36

gMVP

0.63

Mutation Taster

=19/81

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over