chrX-120626774-A-T

Position:

chrX-120626774-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001011551.3(C1GALT1C1):c.393T>A(p.Asp131Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,207,804 control chromosomes in the GnomAD database, including 20,280 homozygotes. There are 87,593 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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. D131N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.16 ( 1382 hom., 5268 hem., cov: 23)

Exomes 𝑓: 0.22 ( 18898 hom. 82325 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: -0.137

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011901557).

BP6

Variant X-120626774-A-T is Benign according to our data. Variant chrX-120626774-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 10792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1GALT1C1	NM_001011551.3 linkuse as main transcript	c.393T>A	p.Asp131Glu	missense_variant	2/2	ENST00000304661.6
C1GALT1C1	NM_152692.5 linkuse as main transcript	c.393T>A	p.Asp131Glu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1C1	ENST00000304661.6 linkuse as main transcript	c.393T>A	p.Asp131Glu	missense_variant	2/2	1	NM_001011551.3	P1
C1GALT1C1	ENST00000371313.2 linkuse as main transcript	c.393T>A	p.Asp131Glu	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

18155

AN:

111450

Hom.:

1383

Cov.:

AF XY:

0.157

AC XY:

5265

AN XY:

33622

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.199

AC:

36224

AN:

181667

Hom.:

2312

AF XY:

0.216

AC XY:

14310

AN XY:

66393

show subpopulations

Gnomad AFR exome

AF:

0.0322

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.224

AC:

245162

AN:

1096300

Hom.:

18898

Cov.:

AF XY:

0.227

AC XY:

82325

AN XY:

361878

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.163

AC:

18150

AN:

111504

Hom.:

1382

Cov.:

AF XY:

0.156

AC XY:

5268

AN XY:

33686

show subpopulations

Gnomad4 AFR

AF:

0.0353

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.213

Hom.:

5927

Bravo

AF:

0.150

TwinsUK

AF:

0.243

AC:

900

ALSPAC

AF:

0.239

AC:

691

ESP6500AA

AF:

0.0407

AC:

156

ESP6500EA

AF:

0.228

AC:

1532

ExAC

AF:

0.202

AC:

24517

EpiCase

AF:

0.221

EpiControl

AF:

0.231

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Polyagglutinable erythrocyte syndrome

Pathogenic:1Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 27, 2005	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 10, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

C1GALT1C1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.0

DANN

Benign

0.61

DEOGEN2

Benign

0.075

T;T

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.45

.;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.45

N;N

MutationTaster

Benign

0.46

P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.27

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.029

MutPred

0.14

Gain of ubiquitination at K132 (P = 0.107);Gain of ubiquitination at K132 (P = 0.107);

MPC

0.26

ClinPred

0.0049

GERP RS

1.5

Varity_R

0.052

gMVP

0.45

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