Genetic Variant ENST00000238018.8:c.1399C>T (chr9-72250787-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000238018.8(GDA):c.1399C>T(p.Pro467Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,608,784 control chromosomes in the GnomAD database, including 644 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.020 ( 51 hom., cov: 32)

Exomes 𝑓: 0.026 ( 593 hom. )

Consequence

GDA
ENST00000238018.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.18

Publications

6 publications found

Variant links:

Genes affected

GDA (HGNC:4212): (guanine deaminase) This gene encodes an enzyme responsible for the hydrolytic deamination of guanine. Studies in rat ortholog suggest this gene plays a role in microtubule assembly. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

GDA links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037838817).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0199 (3030/152256) while in subpopulation NFE AF = 0.0299 (2031/68014). AF 95% confidence interval is 0.0288. There are 51 homozygotes in GnomAd4. There are 1418 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 51 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000238018.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDA	NM_004293.5	MANE Select	c.*2445C>T		3_prime_UTR	Exon 14 of 14	NP_004284.1	Q9Y2T3-1
GDA	NM_001242505.3		c.1399C>T	p.Pro467Ser	missense	Exon 15 of 16	NP_001229434.1	Q9Y2T3-3
GDA	NM_001351572.2		c.1399C>T	p.Pro467Ser	missense	Exon 15 of 16	NP_001338501.1	Q9Y2T3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDA	ENST00000238018.8	TSL:1	c.1399C>T	p.Pro467Ser	missense	Exon 15 of 16	ENSP00000238018.4	Q9Y2T3-3
GDA	ENST00000358399.8	TSL:1 MANE Select	c.*2445C>T		3_prime_UTR	Exon 14 of 14	ENSP00000351170.4	Q9Y2T3-1
GDA	ENST00000475764.5	TSL:1	n.*102C>T		non_coding_transcript_exon	Exon 15 of 16	ENSP00000436619.1	Q9Y2T3-1

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3030

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00538

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0274

GnomAD2 exomes

AF:

0.0203

AC:

4937

AN:

243642

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0246

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0257

AC:

37366

AN:

1456528

Hom.:

593

Cov.:

AF XY:

0.0252

AC XY:

18281

AN XY:

724818

show subpopulations

African (AFR)

AF:

0.00455

AC:

152

AN:

33388

American (AMR)

AF:

0.0226

AC:

1012

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

660

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00565

AC:

487

AN:

86170

European-Finnish (FIN)

AF:

0.0184

AC:

959

AN:

52258

Middle Eastern (MID)

AF:

0.0229

AC:

132

AN:

5764

European-Non Finnish (NFE)

AF:

0.0295

AC:

32647

AN:

1108288

Other (OTH)

AF:

0.0219

AC:

1317

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

1638

3276

4913

6551

8189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1190

2380

3570

4760

5950

<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:

0.0199

AC:

3030

AN:

152256

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1418

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00537

AC:

223

AN:

41558

American (AMR)

AF:

0.0287

AC:

439

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00352

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0135

AC:

143

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2031

AN:

68014

Other (OTH)

AF:

0.0275

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0277

Hom.:

208

Bravo

AF:

0.0206

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0314

AC:

121

ESP6500AA

AF:

0.00285

AC:

ESP6500EA

AF:

0.0286

AC:

114

ExAC

AF:

0.0197

AC:

2280

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0318

EpiControl

AF:

0.0334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.38

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

PhyloP100

-2.2

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.17

REVEL

Benign

0.040

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.16

MPC

0.36

ClinPred

0.0039

GERP RS

-4.2

gMVP

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over