10-8051222-T-A

Variant names:

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

Variant summary

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

The ENST00000420815.5(GATA3-AS1):​n.401+52A>T 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-AS1 ENST00000420815.5 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)

ENSG00000232638 (HGNC:):

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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3-AS1	NR_024256.1	n.1442A>T		non_coding_transcript_exon_variant	Exon 2 of 2
GATA3-AS1	NR_104329.1	n.502A>T		non_coding_transcript_exon_variant	Exon 2 of 3
GATA3	NM_001441115.1	c.-369-4065T>A		intron_variant	Intron 1 of 5		NP_001428044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3-AS1	ENST00000420815.5	n.401+52A>T		intron_variant	Intron 2 of 2	1
GATA3-AS1	ENST00000438755.1	n.426+27A>T		intron_variant	Intron 2 of 2	1
GATA3-AS1	ENST00000355358.1	n.1442A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

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 = 0.000000), 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 v4.3

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;