rs9944560

Variant names:

• chr18-22184305-T-C
• rs9944560
• NM_005257.6:c.1620+1262T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005257.6(GATA6):​c.1620+1262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,554 control chromosomes in the GnomAD database, including 6,588 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (6588 hom., cov: 32)
• Consequence: GATA6 NM_005257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 1 publications found

Genes affected

GATA6 (HGNC:4174): (GATA binding protein 6) This gene is a member of a small family of zinc finger transcription factors that play an important role in the regulation of cellular differentiation and organogenesis during vertebrate development. This gene is expressed during early embryogenesis and localizes to endo- and mesodermally derived cells during later embryogenesis and thereby plays an important role in gut, lung, and heart development. Mutations in this gene are associated with several congenital defects. [provided by RefSeq, Mar 2012]

GATA6 Gene-Disease associations (from GenCC):

• atrial septal defect 9

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, G2P
• atrioventricular septal defect 5

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics, Genomics England PanelApp
• metabolic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• tetralogy of fallot

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• conotruncal heart malformations

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005257.6. 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
	GATA6	NM_005257.6	MANE Select	c.1620+1262T>C		intron	N/A	NP_005248.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA6	ENST00000269216.10	TSL:1 MANE Select	c.1620+1262T>C		intron	N/A	ENSP00000269216.3	Q92908-1
	GATA6	ENST00000581694.1	TSL:1	c.1620+1262T>C		intron	N/A	ENSP00000462313.1	Q92908-1
	GATA6	ENST00000853536.1		c.1728+1262T>C		intron	N/A	ENSP00000523595.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26315 AN: 151438 Hom.: 6557 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.132

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.174 AC: 26403 AN: 151554 Hom.: 6588 Cov.: 32 AF XY: 0.171 AC XY: 12650 AN XY: 74096

African (AFR) AF: 0.553 AC: 22841 AN: 41334

American (AMR) AF: 0.0940 AC: 1433 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3466

East Asian (EAS) AF: 0.0861 AC: 446 AN: 5178

South Asian (SAS) AF: 0.0357 AC: 172 AN: 4824

European-Finnish (FIN) AF: 0.0258 AC: 270 AN: 10468

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 868 AN: 67760

Other (OTH) AF: 0.131 AC: 275 AN: 2100

Alfa AF: 0.158 Hom.: 609

Bravo AF: 0.196

Asia WGS AF: 0.102 AC: 355 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.45
PhyloP100		-2.1
Mutation Taster		=100/0	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: rs9944560; hg19: chr18-19764266;