chrX-120626501-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001011551.3(C1GALT1C1):c.666G>C(p.Gln222His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,210,871 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 175 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q222R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 8 hem., cov: 24)

Exomes 𝑓: 0.00033 ( 0 hom. 167 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.46

Publications

4 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052019745).

BP6

Variant X-120626501-C-G is Benign according to our data. Variant chrX-120626501-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2051173.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

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.666G>C	p.Gln222His	missense	Exon 2 of 2	NP_001011551.1	Q96EU7
	C1GALT1C1	NM_152692.5		c.666G>C	p.Gln222His	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.666G>C	p.Gln222His	missense	Exon 2 of 2	ENSP00000304364.5	Q96EU7
C1GALT1C1	ENST00000371313.2	TSL:1	c.666G>C	p.Gln222His	missense	Exon 3 of 3	ENSP00000360363.2	Q96EU7
C1GALT1C1	ENST00000899457.1		c.666G>C	p.Gln222His	missense	Exon 2 of 2	ENSP00000569516.1

Frequencies

GnomAD3 genomes

AF:

0.000222

AC:

AN:

112692

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:

0.00286

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000319

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000393

AC:

AN:

183344

AF XY:

0.000560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000325

AC:

357

AN:

1098124

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

167

AN XY:

363498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.000199

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19382

East Asian (EAS)

AF:

0.00

AC:

AN:

30196

South Asian (SAS)

AF:

0.00181

AC:

AN:

54142

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40491

Middle Eastern (MID)

AF:

0.00169

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000271

AC:

228

AN:

842077

Other (OTH)

AF:

0.000325

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000222

AC:

AN:

112747

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

34899

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31118

American (AMR)

AF:

0.00

AC:

AN:

10629

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3599

South Asian (SAS)

AF:

0.00287

AC:

AN:

2791

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6149

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000319

AC:

AN:

53363

Other (OTH)

AF:

0.00

AC:

AN:

1542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000397

Hom.:

Bravo

AF:

0.000200

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000494

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

C1GALT1C1-related disorder (1)

Polyagglutinable erythrocyte syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Uncertain

0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.025

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

PhyloP100

2.5

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.28

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Polyphen

0.32

Vest4

0.28

MutPred

0.67

Gain of sheet (P = 0.0827)

MVP

0.85

MPC

0.93

ClinPred

0.15

GERP RS

3.7

Varity_R

0.64

gMVP

0.95

Mutation Taster

=94/6

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