rs6061243

Variant names:

• chr20-62465397-C-G
• rs6061243
• NM_080473.5:c.981G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-62465397-C-G
• chr20-62465397-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_080473.5(GATA5):​c.981G>C​(p.Ser327Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,604,128 control chromosomes in the GnomAD database, including 198,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22497 hom., cov: 33)
  • Exomes 𝑓: 0.49 (176435 hom.)
• Consequence: GATA5 NM_080473.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.05
• Publications: 19 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 20-62465397-C-G is Benign according to our data. Variant chr20-62465397-C-G is described in ClinVar as Benign. ClinVar VariationId is 1174882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 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.981G>C	p.Ser327Ser	synonymous	Exon 6 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.981G>C	p.Ser327Ser	synonymous	Exon 6 of 7	ENSP00000252997.2	Q9BWX5
	GATA5	ENST00000914293.1		c.1137G>C	p.Ser379Ser	synonymous	Exon 6 of 7	ENSP00000584352.1
	GATA5	ENST00000861188.1		c.981G>C	p.Ser327Ser	synonymous	Exon 6 of 7	ENSP00000531247.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81325 AN: 151754 Hom.: 22458 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.530

GnomAD2 exomes AF: 0.486 AC: 118556 AN: 243820 AF XY: 0.481

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.460

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.481

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.491 AC: 713576 AN: 1452256 Hom.: 176435 Cov.: 44 AF XY: 0.489 AC XY: 353288 AN XY: 722564

African (AFR) AF: 0.671 AC: 22405 AN: 33412

American (AMR) AF: 0.465 AC: 20690 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10896 AN: 25968

East Asian (EAS) AF: 0.536 AC: 21192 AN: 39548

South Asian (SAS) AF: 0.434 AC: 37401 AN: 86120

European-Finnish (FIN) AF: 0.482 AC: 22747 AN: 47222

Middle Eastern (MID) AF: 0.429 AC: 2426 AN: 5656

European-Non Finnish (NFE) AF: 0.492 AC: 546147 AN: 1109736

Other (OTH) AF: 0.494 AC: 29672 AN: 60106

GnomAD4 genome AF: 0.536 AC: 81421 AN: 151872 Hom.: 22497 Cov.: 33 AF XY: 0.533 AC XY: 39599 AN XY: 74238

African (AFR) AF: 0.669 AC: 27743 AN: 41464

American (AMR) AF: 0.506 AC: 7728 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2518 AN: 5116

South Asian (SAS) AF: 0.448 AC: 2160 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4776 AN: 10542

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.491 AC: 33339 AN: 67868

Other (OTH) AF: 0.532 AC: 1121 AN: 2108

Alfa AF: 0.417 Hom.: 1973

Bravo AF: 0.543

Asia WGS AF: 0.502 AC: 1749 AN: 3478

EpiCase AF: 0.486

EpiControl AF: 0.486

ClinVar

ClinVar submissions

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	-0.77
CADD	Benign	6.8
DANN	Benign	0.52
PhyloP100		1.0
Mutation Taster		=45/55	disease causing

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: rs6061243; hg19: chr20-61040453; COSMIC: COSV53345496;