Genetic Variant C1GALT1C1:p.Gly252Glu (chrX-120626412-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001011551.3(C1GALT1C1):c.755G>A(p.Gly252Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,210,737 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 0 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Publications

0 publications found

Variant links:

Genes affected

C1GALT1C1 (HGNC:24338): (C1GALT1 specific chaperone 1) This gene encodes a type II transmembrane protein that is similar to the core 1 beta1,3-galactosyltransferase 1, which catalyzes the synthesis of the core-1 structure, also known as Thomsen-Friedenreich antigen, on O-linked glycans. This gene product lacks the galactosyltransferase activity itself, but instead acts as a molecular chaperone required for the folding, stability and full activity of the core 1 beta1,3-galactosyltransferase 1. Mutations in this gene have been associated with Tn syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Dec 2009]

C1GALT1C1 Gene-Disease associations (from GenCC):

hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

C1GALT1C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07656467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011551.3. 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
	C1GALT1C1	NM_001011551.3	MANE Select	c.755G>A	p.Gly252Glu	missense	Exon 2 of 2	NP_001011551.1	Q96EU7
	C1GALT1C1	NM_152692.5		c.755G>A	p.Gly252Glu	missense	Exon 3 of 3	NP_689905.1	Q96EU7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1GALT1C1	ENST00000304661.6	TSL:1 MANE Select	c.755G>A	p.Gly252Glu	missense	Exon 2 of 2	ENSP00000304364.5	Q96EU7
C1GALT1C1	ENST00000371313.2	TSL:1	c.755G>A	p.Gly252Glu	missense	Exon 3 of 3	ENSP00000360363.2	Q96EU7
C1GALT1C1	ENST00000899457.1		c.755G>A	p.Gly252Glu	missense	Exon 2 of 2	ENSP00000569516.1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112961

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000963

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

183055

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000380

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363164

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26395

American (AMR)

AF:

0.00

AC:

AN:

35190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19369

East Asian (EAS)

AF:

0.00

AC:

AN:

30192

South Asian (SAS)

AF:

0.00

AC:

AN:

54115

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841793

Other (OTH)

AF:

0.00

AC:

AN:

46078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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

AF:

0.0000266

AC:

AN:

112961

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35111

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

31143

American (AMR)

AF:

0.00

AC:

AN:

10679

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3619

South Asian (SAS)

AF:

0.00

AC:

AN:

2809

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6197

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53395

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.059

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.42

M_CAP

Benign

0.010

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.11

PhyloP100

2.3

PrimateAI

Benign

0.45

PROVEAN

Benign

0.25

REVEL

Benign

0.13

Sift

Benign

0.61

Sift4G

Benign

0.29

Polyphen

0.0030

Vest4

0.086

MVP

0.66

MPC

0.36

ClinPred

0.034

GERP RS

5.5

Varity_R

0.19

gMVP

0.86

Mutation Taster

=66/34

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over