rs412359

Variant names:

• chr10-8055598-C-T
• rs412359
• NM_001002295.2:c.-58C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-8055598-C-T
• chr10-8055598-C-A
• chr10-8055598-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.-58C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,532,416 control chromosomes in the GnomAD database, including 492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (274 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (218 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.74
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 10-8055598-C-T is Benign according to our data. Variant chr10-8055598-C-T is described in ClinVar as Benign. ClinVar VariationId is 301114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002295.2. 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_001002295.2	MANE Select	c.-58C>T		5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-58C>T		5_prime_UTR	Exon 2 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.-58C>T		5_prime_UTR	Exon 3 of 7	NP_001428045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-58C>T		5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-58C>T		5_prime_UTR	Exon 2 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-58C>T		5_prime_UTR	Exon 3 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5084 AN: 151882 Hom.: 274 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0202

GnomAD4 exome AF: 0.00347 AC: 4792 AN: 1380420 Hom.: 218 Cov.: 33 AF XY: 0.00299 AC XY: 2036 AN XY: 680854

African (AFR) AF: 0.119 AC: 3705 AN: 31210

American (AMR) AF: 0.00746 AC: 263 AN: 35252

Ashkenazi Jewish (ASJ) AF: 0.000525 AC: 13 AN: 24768

East Asian (EAS) AF: 0.00 AC: 0 AN: 35500

South Asian (SAS) AF: 0.000319 AC: 25 AN: 78434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37458

Middle Eastern (MID) AF: 0.00791 AC: 35 AN: 4426

European-Non Finnish (NFE) AF: 0.000270 AC: 291 AN: 1075884

Other (OTH) AF: 0.00800 AC: 460 AN: 57488

GnomAD4 genome AF: 0.0335 AC: 5089 AN: 151996 Hom.: 274 Cov.: 31 AF XY: 0.0330 AC XY: 2450 AN XY: 74326

African (AFR) AF: 0.116 AC: 4808 AN: 41390

American (AMR) AF: 0.0126 AC: 192 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000589 AC: 40 AN: 67962

Other (OTH) AF: 0.0200 AC: 42 AN: 2104

Alfa AF: 0.00617 Hom.: 7

Bravo AF: 0.0373

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.98
PhyloP100		2.7
Mutation Taster		=300/0	polymorphism (auto)

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: rs412359; hg19: chr10-8097561;