NM_001308093.3:c.12C>G

Variant names:

• chr8-11708324-C-G
• rs1247823780
• NM_001308093.3:c.12C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001308093.3(GATA4):​c.12C>G​(p.Ser4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA4 NM_001308093.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.12C>G	p.Ser4Arg	missense_variant	Exon 2 of 7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.12C>G	p.Ser4Arg	missense_variant	Exon 2 of 7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.;D;.;.;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Pathogenic	0.98	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	.;.;M;.;M;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.1	.;.;N;D;N;.
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0020	.;.;D;D;D;.
Sift4G	Pathogenic	0.0	.;D;D;D;D;D
Polyphen		1.0	.;.;D;.;.;.
Vest4		0.59, 0.64, 0.56
MutPred		0.68		Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);
MVP		0.85
MPC		0.074
ClinPred		0.96	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1247823780; hg19: chr8-11565833;