18-22172111-TACCACCACCACCACC-TACC

Position:

• chr18-22172111-TACCACCACCACCACC-TACC

Variant summary

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

The NM_005257.6(GATA6):​c.987_998del​(p.His330_His333del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000136 in 1,463,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (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 GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA6	NM_005257.6	c.987_998del	p.His330_His333del	inframe_deletion	2/7	ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.987_998del	p.His330_His333del	inframe_deletion	2/7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.987_998del	p.His330_His333del	inframe_deletion	2/7	1	NM_005257.6	ENSP00000269216	P1
GATA6	ENST00000581694.1	c.987_998del	p.His330_His333del	inframe_deletion	1/6	1		ENSP00000462313	P1

Frequencies

GnomAD3 genomes AF: 0.0000734 AC: 11 AN: 149902 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.000295

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000746

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000268 AC: 13 AN: 48518 Hom.: 0 AF XY: 0.000268 AC XY: 7 AN XY: 26132

Gnomad AFR exome AF: 0.000466

Gnomad AMR exome AF: 0.0000957

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000932

Gnomad SAS exome AF: 0.000130

Gnomad FIN exome AF: 0.00221

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 188 AN: 1313804 Hom.: 0 AF XY: 0.000135 AC XY: 87 AN XY: 644914

Gnomad4 AFR exome AF: 0.0000343

Gnomad4 AMR exome AF: 0.0000619

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000124

Gnomad4 SAS exome AF: 0.0000554

Gnomad4 FIN exome AF: 0.000716

Gnomad4 NFE exome AF: 0.000147

Gnomad4 OTH exome AF: 0.0000736

GnomAD4 genome AF: 0.0000733 AC: 11 AN: 149998 Hom.: 0 Cov.: 32 AF XY: 0.0000683 AC XY: 5 AN XY: 73208

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.000295

Gnomad4 NFE AF: 0.0000746

Gnomad4 OTH AF: 0.00

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

Labcorp Genetics (formerly Invitae), Labcorp

Oct 22, 2023

This variant, c.987_998del, results in the deletion of 4 amino acid(s) of the GATA6 protein (p.His330_His333del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GATA6-related conditions. ClinVar contains an entry for this variant (Variation ID: 655336). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

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;