X-48791170-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002049.4(GATA1):c.61C>T(p.Pro21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,207,093 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000016 ( 0 hom. 8 hem. )

Consequence

GATA1
NM_002049.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06903994).

BS2

High Hemizygotes in GnomAdExome4 at 8 AR,XL,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002049.4. 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
	GATA1	NM_002049.4	MANE Select	c.61C>T	p.Pro21Ser	missense	Exon 2 of 6	NP_002040.1	P15976-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATA1	ENST00000376670.9	TSL:1 MANE Select	c.61C>T	p.Pro21Ser	missense	Exon 2 of 6	ENSP00000365858.3	P15976-1
GATA1	ENST00000696450.1		c.61C>T	p.Pro21Ser	missense	Exon 2 of 6	ENSP00000512637.1	A0A8Q3SIN3
GATA1	ENST00000376665.4	TSL:5	c.61C>T	p.Pro21Ser	missense	Exon 2 of 6	ENSP00000365853.3	B7WNQ9

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000115

AC:

AN:

174470

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000260

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1095061

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

360875

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26374

American (AMR)

AF:

0.00

AC:

AN:

34943

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19242

East Asian (EAS)

AF:

0.00

AC:

AN:

30158

South Asian (SAS)

AF:

0.00

AC:

AN:

53348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

840532

Other (OTH)

AF:

0.0000218

AC:

AN:

45974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00000893

AC:

AN:

112032

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34204

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

30854

American (AMR)

AF:

0.00

AC:

AN:

10717

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3536

South Asian (SAS)

AF:

0.00

AC:

AN:

2705

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6133

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53002

Other (OTH)

AF:

0.00

AC:

AN:

1515

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Uncertain

0.43

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.069

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

0.0

PhyloP100

2.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

REVEL

Benign

0.27

Sift

Benign

0.51

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.099

MutPred

0.34

Gain of glycosylation at P21 (P = 0.0121)

MVP

0.38

MPC

0.045

ClinPred

0.015

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.041

gMVP

0.28

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over