rs782188059

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002049.4(GATA1):c.64G>A(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,094,774 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22G) has been classified as Benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000064 ( 0 hom. 2 hem. )

Consequence

GATA1
NM_002049.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.668

Publications

0 publications found

Variant links:

Genes affected

GATA1 (HGNC:4170): (GATA binding protein 1) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia. [provided by RefSeq, Jul 2008]

GATA1 Gene-Disease associations (from GenCC):

GATA1-Related X-Linked Cytopenia
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
thrombocytopenia, X-linked, with or without dyserythropoietic anemia
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
beta-thalassemia-X-linked thrombocytopenia syndrome
Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cutaneous porphyria
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
thrombocytopenia with congenital dyserythropoietic anemia
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked dyserythropoetic anemia with abnormal platelets and neutropenia
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

GATA1 links:

ENSG00000232828 (HGNC:):

ENSG00000232828 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11292681).

BP6

Variant X-48791173-G-A is Benign according to our data. Variant chrX-48791173-G-A is described in ClinVar as Benign. ClinVar VariationId is 533697.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 AR,XL,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA1	NM_002049.4 link	c.64G>A	p.Ala22Thr	missense_variant	Exon 2 of 6	ENST00000376670.9	NP_002040.1	P15976-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA1	ENST00000376670.9 link	c.64G>A	p.Ala22Thr	missense_variant	Exon 2 of 6	1	NM_002049.4	ENSP00000365858.3		P15976-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000575

AC:

AN:

174051

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000138

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1094774

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

360604

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26362

American (AMR)

AF:

0.00

AC:

AN:

34934

Ashkenazi Jewish (ASJ)

AF:

0.000260

AC:

AN:

19242

East Asian (EAS)

AF:

0.00

AC:

AN:

30164

South Asian (SAS)

AF:

0.00

AC:

AN:

53285

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40347

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

840354

Other (OTH)

AF:

0.00

AC:

AN:

45962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis

Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.66

T;T

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.11

T;T

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.67

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.75

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.21

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.59

P;.

Vest4

0.088

MutPred

0.090

Gain of glycosylation at A22 (P = 0.0118);Gain of glycosylation at A22 (P = 0.0118);

MVP

0.66

MPC

0.048

ClinPred

0.14

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.080

gMVP

0.23

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over