rs6061243

chr20-62465397-C-Gchr20-62465397-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_080473.5(GATA5):c.981G>C(p.Ser327=) 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:5
• Conservation: PhyloP100: 1.05

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 Benign. Variant got -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 id is 1174882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62465397-C-G is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA5	NM_080473.5	c.981G>C	p.Ser327=	synonymous_variant	6/7	ENST00000252997.3
GATA5	XM_006723699.3	c.981G>C	p.Ser327=	synonymous_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA5	ENST00000252997.3	c.981G>C	p.Ser327=	synonymous_variant	6/7	1	NM_080473.5	P1

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

GnomAD3 exomes AF: 0.486 AC: 118556 AN: 243820 Hom.: 29339 AF XY: 0.481 AC XY: 63824 AN XY: 132648

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 SAS exome AF: 0.436

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

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.536

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.494

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

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.532

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

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Congenital heart defects, multiple types, 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.8
Dann	Benign	0.52

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

LitVar

Other links and lift over

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