rs1275066172

chr18-22171906-A-Gchr18-22171906-A-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005257.6(GATA6):c.762A>G(p.Ser254=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000586 in 1,161,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: GATA6 NM_005257.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 18-22171906-A-G is Benign according to our data. Variant chr18-22171906-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 472915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.
• BS2: High AC in GnomAd at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA6	NM_005257.6	c.762A>G	p.Ser254=	synonymous_variant	2/7	ENST00000269216.10
GATA6	XM_047437483.1	c.762A>G	p.Ser254=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA6	ENST00000269216.10	c.762A>G	p.Ser254=	synonymous_variant	2/7	1	NM_005257.6	P1
GATA6	ENST00000581694.1	c.762A>G	p.Ser254=	synonymous_variant	1/6	1		P1

Frequencies

GnomAD3 genomes AF: 0.0000336 AC: 5 AN: 148688 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000600

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000612 AC: 62 AN: 1012534 Hom.: 0 Cov.: 29 AF XY: 0.0000608 AC XY: 29 AN XY: 477112

Gnomad4 AFR exome AF: 0.0000981

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000893

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000593

Gnomad4 OTH exome AF: 0.000156

GnomAD4 genome AF: 0.0000403 AC: 6 AN: 148792 Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 3 AN XY: 72554

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000600

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrioventricular septal defect 5 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 22, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.2
Dann	Benign	0.39

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: rs1275066172; hg19: chr18-19751867;