rs6587239

Variant names:

• chr20-62465895-C-A
• NM_080473.5:c.852G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-62465895-C-A
• chr20-62465895-C-G
• chr20-62465895-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	c.852G>T	p.Lys284Asn	missense_variant	Exon 5 of 7	ENST00000252997.3	NP_536721.1
GATA5	XM_006723699.3	c.852G>T	p.Lys284Asn	missense_variant	Exon 5 of 7		XP_006723762.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443550 Hom.: 0 Cov.: 44 AF XY: 0.00000140 AC XY: 1 AN XY: 716176

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: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.32		Loss of methylation at K284 (P = 0.0025);
MVP		1.0
MPC		0.49
ClinPred		0.99	D
GERP RS		1.9
Varity_R		0.36
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-61040951;