rs387906769

Variant names:

• chr8-11708799-C-G
• rs387906769
• NM_001308093.3:c.487C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11708799-C-G
• chr8-11708799-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001308093.3(GATA4):​c.487C>G​(p.Pro163Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,324,970 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P163S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: GATA4 NM_001308093.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.487C>G	p.Pro163Ala	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.487C>G	p.Pro163Ala	missense_variant	Exon 2 of 7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1324970 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 653204

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 26508

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 28106

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 22790

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 29742

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 72980

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 32886

Gnomad4 NFE exome AF: 9.50e-7 AC: 1 AN: 1053140

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 54930

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.86	D;.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Pathogenic	1.0	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.5	N;N;.
REVEL	Uncertain	0.61
Sift	Benign	0.082	T;T;.
Sift4G	Benign	0.097	T;T;T
Polyphen		0.45	P;.;.
Vest4		0.30
MutPred		0.56		Loss of glycosylation at P163 (P = 0.0321);Loss of glycosylation at P163 (P = 0.0321);.;
MVP		0.83
MPC		1.4
ClinPred		0.60	D
GERP RS		3.7
Varity_R		0.10
gMVP		0.65
Mutation Taster		=70/30	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

Publications

LitVar

Other links and lift over

dbSNP: rs387906769; hg19: chr8-11566308;