NM_001308093.3:c.72C>T

Variant names:

• chr8-11708384-C-T
• rs746574040
• NM_001308093.3:c.72C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_001308093.3(GATA4):​c.72C>T​(p.Gly24Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G24G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA4 NM_001308093.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62
• Publications: 0 publications found

Genes affected

GATA4 (HGNC:4173): (GATA binding protein 4) This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GATA4 Gene-Disease associations (from GenCC):

• atrial septal defect 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• structural congenital heart disease, multiple types - GATA4

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• testicular anomalies with or without congenital heart disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• metabolic syndrome

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

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome

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

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

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15273604).
• BP6: Variant 8-11708384-C-T is Benign according to our data. Variant chr8-11708384-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1912751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308093.3. 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
	GATA4	NM_001308093.3	MANE Select	c.72C>T	p.Gly24Gly	synonymous	Exon 2 of 7	NP_001295022.1	P43694-2
	GATA4	NM_002052.5		c.72C>T	p.Gly24Gly	synonymous	Exon 2 of 7	NP_002043.2
	GATA4	NM_001308094.2		c.-6+7606C>T		intron	N/A	NP_001295023.1	B3KUF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	ENST00000532059.6	TSL:1 MANE Select	c.72C>T	p.Gly24Gly	synonymous	Exon 2 of 7	ENSP00000435712.1	P43694-2
	GATA4	ENST00000886854.1		c.72C>T	p.Gly24Gly	synonymous	Exon 2 of 7	ENSP00000556913.1
	GATA4	ENST00000886846.1		c.72C>T	p.Gly24Gly	synonymous	Exon 3 of 8	ENSP00000556905.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atrioventricular septal defect 4 (1)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.7
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.54	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.85	T
PhyloP100		-1.6
Sift4G	Benign	0.19	T
Vest4		0.13
MVP		0.81
ClinPred		0.14	T
GERP RS		-3.6
Mutation Taster		=97/3	polymorphism

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: rs746574040; hg19: chr8-11565893; COSMIC: COSV58732791; COSMIC: COSV58732791;