rs10179904

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000821.7(GGCX):c.1242C>T(p.Thr414Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,666 control chromosomes in the GnomAD database, including 12,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1010 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11544 hom. )

Consequence

GGCX
NM_000821.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.42

Publications

23 publications found

Variant links:

Genes affected

GGCX (HGNC:4247): (gamma-glutamyl carboxylase) This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

GGCX Gene-Disease associations (from GenCC):

body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
vitamin K-dependent clotting factors, combined deficiency of, type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
pulmonary arterial hypertension
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GGCX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-85552984-G-A is Benign according to our data. Variant chr2-85552984-G-A is described in ClinVar as Benign. ClinVar VariationId is 337265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000821.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGCX	NM_000821.7	MANE Select	c.1242C>T	p.Thr414Thr	synonymous	Exon 9 of 15	NP_000812.2
	GGCX	NM_001142269.4		c.1071C>T	p.Thr357Thr	synonymous	Exon 8 of 14	NP_001135741.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GGCX	ENST00000233838.9	TSL:1 MANE Select	c.1242C>T	p.Thr414Thr	synonymous	Exon 9 of 15	ENSP00000233838.3
GGCX	ENST00000689276.1		c.1173C>T	p.Thr391Thr	synonymous	Exon 9 of 15	ENSP00000510012.1
GGCX	ENST00000430215.7	TSL:2	c.1071C>T	p.Thr357Thr	synonymous	Exon 8 of 14	ENSP00000408045.3

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17119

AN:

152174

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0598

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.0789

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.124

GnomAD2 exomes

AF:

0.114

AC:

28726

AN:

251456

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0685

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.0584

Gnomad FIN exome

AF:

0.0801

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.123

AC:

179687

AN:

1461374

Hom.:

11544

Cov.:

AF XY:

0.125

AC XY:

91098

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.110

AC:

3683

AN:

33474

American (AMR)

AF:

0.0719

AC:

3217

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2932

AN:

26134

East Asian (EAS)

AF:

0.0613

AC:

2435

AN:

39698

South Asian (SAS)

AF:

0.189

AC:

16276

AN:

86238

European-Finnish (FIN)

AF:

0.0801

AC:

4279

AN:

53418

Middle Eastern (MID)

AF:

0.136

AC:

787

AN:

5766

European-Non Finnish (NFE)

AF:

0.124

AC:

138290

AN:

1111542

Other (OTH)

AF:

0.129

AC:

7788

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9250

18501

27751

37002

46252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5020

10040

15060

20080

25100

<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:

0.112

AC:

17130

AN:

152292

Hom.:

1010

Cov.:

AF XY:

0.113

AC XY:

8421

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.107

AC:

4452

AN:

41564

American (AMR)

AF:

0.115

AC:

1761

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

429

AN:

3470

East Asian (EAS)

AF:

0.0596

AC:

309

AN:

5186

South Asian (SAS)

AF:

0.186

AC:

896

AN:

4826

European-Finnish (FIN)

AF:

0.0789

AC:

838

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8077

AN:

68016

Other (OTH)

AF:

0.122

AC:

258

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

806

1613

2419

3226

4032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.120

Hom.:

2199

Bravo

AF:

0.113

Asia WGS

AF:

0.122

AC:

424

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Vitamin K-dependent clotting factors, combined deficiency of, type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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

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

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over