rs562588574

Positions:

• chr18-22172111-TACCACCACCACCACC-T
• chr18-22172111-TACCACCACCACCACC-TACC
• chr18-22172111-TACCACCACCACCACC-TACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACC
• chr18-22172111-TACCACCACCACCACC-TACCACCACCACCACCACCACC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005257.6(GATA6):​c.984_998del​(p.His329_His333del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000457 in 1,313,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: GATA6 NM_005257.6 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA6	NM_005257.6	c.984_998del	p.His329_His333del	inframe_deletion	2/7	ENST00000269216.10
GATA6	XM_047437483.1	c.984_998del	p.His329_His333del	inframe_deletion	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA6	ENST00000269216.10	c.984_998del	p.His329_His333del	inframe_deletion	2/7	1	NM_005257.6	P1
GATA6	ENST00000581694.1	c.984_998del	p.His329_His333del	inframe_deletion	1/6	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000457 AC: 6 AN: 1313808 Hom.: 0 AF XY: 0.00000930 AC XY: 6 AN XY: 644914

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000578

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrioventricular septal defect 5 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 29, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with GATA6-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.984_998del, results in the deletion of 5 amino acid(s) of the GATA6 protein (p.His329_His333del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs562588574; hg19: chr18-19752072;