rs369825935

Variant names:

• chr10-8055561-G-T
• rs369825935
• NM_001002295.2:c.-95G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-8055561-G-T
• chr10-8055561-G-A
• chr10-8055561-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001002295.2(GATA3):​c.-95G>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 0.00128 in 1,369,584 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (12 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.888
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-8055561-G-T is Benign according to our data. Variant chr10-8055561-G-T is described in ClinVar as Benign. ClinVar VariationId is 301111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00118 (163/137580) while in subpopulation SAS AF = 0.0151 (61/4040). AF 95% confidence interval is 0.0121. There are 1 homozygotes in GnomAd4. There are 102 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 163 AD gene.

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.-95G>T		5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-95G>T		5_prime_UTR	Exon 2 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.-95G>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.-95G>T		5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-95G>T		5_prime_UTR	Exon 2 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-95G>T		5_prime_UTR	Exon 3 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 163 AN: 137524 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000833

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.00526

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.00182

Gnomad MID AF: 0.0100

Gnomad NFE AF: 0.000620

Gnomad OTH AF: 0.00216

GnomAD4 exome AF: 0.00129 AC: 1595 AN: 1232004 Hom.: 12 Cov.: 20 AF XY: 0.00159 AC XY: 966 AN XY: 607236

African (AFR) AF: 0.000541 AC: 15 AN: 27736

American (AMR) AF: 0.00129 AC: 35 AN: 27144

Ashkenazi Jewish (ASJ) AF: 0.00507 AC: 107 AN: 21102

East Asian (EAS) AF: 0.0000307 AC: 1 AN: 32558

South Asian (SAS) AF: 0.0121 AC: 751 AN: 61908

European-Finnish (FIN) AF: 0.000992 AC: 32 AN: 32264

Middle Eastern (MID) AF: 0.0111 AC: 41 AN: 3690

European-Non Finnish (NFE) AF: 0.000512 AC: 499 AN: 973862

Other (OTH) AF: 0.00220 AC: 114 AN: 51740

GnomAD4 genome AF: 0.00118 AC: 163 AN: 137580 Hom.: 1 Cov.: 31 AF XY: 0.00152 AC XY: 102 AN XY: 67118

African (AFR) AF: 0.0000831 AC: 3 AN: 36108

American (AMR) AF: 0.00135 AC: 19 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.00526 AC: 17 AN: 3232

East Asian (EAS) AF: 0.00 AC: 0 AN: 4830

South Asian (SAS) AF: 0.0151 AC: 61 AN: 4040

European-Finnish (FIN) AF: 0.00182 AC: 17 AN: 9366

Middle Eastern (MID) AF: 0.0109 AC: 3 AN: 274

European-Non Finnish (NFE) AF: 0.000620 AC: 39 AN: 62872

Other (OTH) AF: 0.00214 AC: 4 AN: 1866

Alfa AF: 0.0000819 Hom.: 0

Bravo AF: 0.000835

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		0.89
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs369825935; hg19: chr10-8097524; COSMIC: COSV105912929; COSMIC: COSV105912929;