rs485411

Variant names:

• chr10-8051222-T-A
• rs485411
• ENST00000420815.5:n.401+52A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-8051222-T-A
• chr10-8051222-T-C
• chr10-8051222-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001441115.1(GATA3):​c.-369-4065T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 261,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: GATA3 NM_001441115.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 28 publications found

Genes affected

GATA3-AS1 (HGNC:33786): (GATA3 antisense RNA 1)

GATA3 (HGNC:4172): (GATA binding protein 3) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T-cell development and plays an important role in endothelial cell biology. Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia. [provided by RefSeq, Nov 2009]

GATA3 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ENSG00000232638 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441115.1. 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
	GATA3	NM_001441115.1		c.-369-4065T>A		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.-369-4065T>A		intron	N/A	NP_001428045.1
	GATA3	NM_001441117.1		c.-711-1213T>A		intron	N/A	NP_001428046.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3-AS1	ENST00000420815.5	TSL:1	n.401+52A>T		intron	N/A
	GATA3-AS1	ENST00000438755.1	TSL:1	n.426+27A>T		intron	N/A
	GATA3	ENST00000872595.1		c.-369-4065T>A		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000115 AC: 3 AN: 261800 Hom.: 0 Cov.: 0 AF XY: 0.0000137 AC XY: 2 AN XY: 145762

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6270

American (AMR) AF: 0.00 AC: 0 AN: 22206

Ashkenazi Jewish (ASJ) AF: 0.000134 AC: 1 AN: 7468

East Asian (EAS) AF: 0.00 AC: 0 AN: 7374

South Asian (SAS) AF: 0.0000397 AC: 2 AN: 50420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 128524

Other (OTH) AF: 0.00 AC: 0 AN: 11606

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 92214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.94
DANN	Benign	0.42
PhyloP100		-0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs485411; hg19: chr10-8093185;