rs10179904

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGCX	NM_000821.7 link	c.1242C>T	p.Thr414Thr	synonymous_variant	Exon 9 of 15	ENST00000233838.9	NP_000812.2	P38435-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGCX	ENST00000233838.9 link	c.1242C>T	p.Thr414Thr	synonymous_variant	Exon 9 of 15	1	NM_000821.7	ENSP00000233838.3		P38435-1

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

GnomAD3 exomes

AF:

0.114

AC:

28726

AN:

251456

Hom.:

1875

AF XY:

0.120

AC XY:

16313

AN XY:

135904

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 SAS exome

AF:

0.192

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

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0719

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.0613

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.0801

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.112

AC:

17130

AN:

152292

Hom.:

1010

Cov.:

AF XY:

0.113

AC XY:

8421

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0596

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.0789

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.121

Hom.:

1639

Bravo

AF:

0.113

Asia WGS

AF:

0.122

AC:

424

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over