20-62465895-C-T

Variant names:

• chr20-62465895-C-T
• rs6587239
• NM_080473.5:c.852G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_080473.5(GATA5):​c.852G>A​(p.Lys284Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,594,492 control chromosomes in the GnomAD database, including 193,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (22401 hom., cov: 34)
  • Exomes 𝑓: 0.48 (170827 hom.)
• Consequence: GATA5 NM_080473.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0710
• Publications: 25 publications found

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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 20-62465895-C-T is Benign according to our data. Variant chr20-62465895-C-T is described in ClinVar as Benign. ClinVar VariationId is 1174638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080473.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA5	NM_080473.5	MANE Select	c.852G>A	p.Lys284Lys	synonymous	Exon 5 of 7	NP_536721.1	Q9BWX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA5	ENST00000252997.3	TSL:1 MANE Select	c.852G>A	p.Lys284Lys	synonymous	Exon 5 of 7	ENSP00000252997.2	Q9BWX5
	GATA5	ENST00000914293.1		c.1008G>A	p.Lys336Lys	synonymous	Exon 5 of 7	ENSP00000584352.1
	GATA5	ENST00000861188.1		c.852G>A	p.Lys284Lys	synonymous	Exon 5 of 7	ENSP00000531247.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81069 AN: 152030 Hom.: 22362 Cov.: 34

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.530

GnomAD2 exomes AF: 0.474 AC: 103051 AN: 217526 AF XY: 0.469

Gnomad AFR exome AF: 0.664

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.444

Gnomad FIN exome AF: 0.459

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.485 AC: 699016 AN: 1442344 Hom.: 170827 Cov.: 44 AF XY: 0.482 AC XY: 344976 AN XY: 715542

African (AFR) AF: 0.674 AC: 22367 AN: 33178

American (AMR) AF: 0.461 AC: 19447 AN: 42184

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 10668 AN: 25738

East Asian (EAS) AF: 0.508 AC: 19805 AN: 38980

South Asian (SAS) AF: 0.432 AC: 35891 AN: 83174

European-Finnish (FIN) AF: 0.471 AC: 24257 AN: 51524

Middle Eastern (MID) AF: 0.431 AC: 2451 AN: 5684

European-Non Finnish (NFE) AF: 0.485 AC: 535134 AN: 1102272

Other (OTH) AF: 0.486 AC: 28996 AN: 59610

GnomAD4 genome AF: 0.533 AC: 81162 AN: 152148 Hom.: 22401 Cov.: 34 AF XY: 0.530 AC XY: 39453 AN XY: 74370

African (AFR) AF: 0.673 AC: 27954 AN: 41536

American (AMR) AF: 0.505 AC: 7735 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2388 AN: 5154

South Asian (SAS) AF: 0.445 AC: 2147 AN: 4824

European-Finnish (FIN) AF: 0.449 AC: 4759 AN: 10588

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33038 AN: 67956

Other (OTH) AF: 0.531 AC: 1122 AN: 2114

Alfa AF: 0.493 Hom.: 40289

Bravo AF: 0.541

Asia WGS AF: 0.490 AC: 1707 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Congenital heart defects, multiple types, 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.8
DANN	Benign	0.53
PhyloP100		-0.071
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6587239; hg19: chr20-61040951; COSMIC: COSV53345233;