chrX-120626739-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001011551.3(C1GALT1C1):c.428C>T(p.Ala143Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,209,784 control chromosomes in the GnomAD database, including 365 homozygotes. There are 9,445 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 23 hom., 757 hem., cov: 23)

Exomes 𝑓: 0.024 ( 342 hom. 8688 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.67

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009571731).

BP6

Variant X-120626739-G-A is Benign according to our data. Variant chrX-120626739-G-A is described in ClinVar as [Benign]. Clinvar id is 460285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0201 (2255/111944) while in subpopulation NFE AF = 0.0261 (1390/53196). AF 95% confidence interval is 0.025. There are 23 homozygotes in GnomAd4. There are 757 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1GALT1C1	NM_001011551.3 link	c.428C>T	p.Ala143Val	missense_variant	Exon 2 of 2	ENST00000304661.6	NP_001011551.1	Q96EU7
C1GALT1C1	NM_152692.5 link	c.428C>T	p.Ala143Val	missense_variant	Exon 3 of 3		NP_689905.1	Q96EU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1GALT1C1	ENST00000304661.6 link	c.428C>T	p.Ala143Val	missense_variant	Exon 2 of 2	1	NM_001011551.3	ENSP00000304364.5		Q96EU7
C1GALT1C1	ENST00000371313.2 link	c.428C>T	p.Ala143Val	missense_variant	Exon 3 of 3	1		ENSP00000360363.2		Q96EU7

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

2256

AN:

111891

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.00875

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00552

Gnomad FIN

AF:

0.0973

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0261

Gnomad OTH

AF:

0.0146

GnomAD2 exomes

AF:

0.0223

AC:

4084

AN:

182776

AF XY:

0.0227

show subpopulations

Gnomad AFR exome

AF:

0.00337

Gnomad AMR exome

AF:

0.00693

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0956

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0243

AC:

26698

AN:

1097840

Hom.:

342

Cov.:

AF XY:

0.0239

AC XY:

8688

AN XY:

363234

show subpopulations

Gnomad4 AFR exome

AF:

0.00265

AC:

AN:

26393

Gnomad4 AMR exome

AF:

0.00723

AC:

254

AN:

35145

Gnomad4 ASJ exome

AF:

0.0125

AC:

242

AN:

19364

Gnomad4 EAS exome

AF:

0.0000994

AC:

AN:

30191

Gnomad4 SAS exome

AF:

0.00772

AC:

418

AN:

54122

Gnomad4 FIN exome

AF:

0.0880

AC:

3566

AN:

40518

Gnomad4 NFE exome

AF:

0.0251

AC:

21146

AN:

841891

Gnomad4 Remaining exome

AF:

0.0213

AC:

982

AN:

46081

Heterozygous variant carriers

1087

2175

3262

4350

5437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.0201

AC:

2255

AN:

111944

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

757

AN XY:

34118

show subpopulations

Gnomad4 AFR

AF:

0.00288

AC:

0.00287886

AN:

0.00287886

Gnomad4 AMR

AF:

0.0110

AC:

0.0109513

AN:

0.0109513

Gnomad4 ASJ

AF:

0.0144

AC:

0.0143722

AN:

0.0143722

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00554

AC:

0.00554119

AN:

0.00554119

Gnomad4 FIN

AF:

0.0973

AC:

0.0973481

AN:

0.0973481

Gnomad4 NFE

AF:

0.0261

AC:

0.0261298

AN:

0.0261298

Gnomad4 OTH

AF:

0.0144

AC:

0.0144168

AN:

0.0144168

Heterozygous variant carriers

153

230

306

383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0252

Hom.:

427

Bravo

AF:

0.0142

TwinsUK

AF:

0.0256

AC:

ALSPAC

AF:

0.0280

AC:

ESP6500AA

AF:

0.00469

AC:

ESP6500EA

AF:

0.0248

AC:

167

ExAC

AF:

0.0216

AC:

2623

EpiCase

AF:

0.0228

EpiControl

AF:

0.0196

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Polyagglutinable erythrocyte syndrome

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

.;D

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.16

B;B

Vest4

0.20

MPC

0.59

ClinPred

0.019

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.93

Mutation Taster

=42/58

polymorphism (auto)

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