NM_001011551.3:c.302G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001011551.3(C1GALT1C1):c.302G>A(p.Ser101Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00739 in 1,209,810 control chromosomes in the GnomAD database, including 31 homozygotes. There are 2,754 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., 139 hem., cov: 23)

Exomes 𝑓: 0.0077 ( 29 hom. 2615 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.70

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008848816).

BP6

Variant X-120626865-C-T is Benign according to our data. Variant chrX-120626865-C-T is described in ClinVar as [Benign]. Clinvar id is 791741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120626865-C-T is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1GALT1C1	NM_001011551.3 link	c.302G>A	p.Ser101Asn	missense_variant	Exon 2 of 2	ENST00000304661.6	NP_001011551.1	Q96EU7
C1GALT1C1	NM_152692.5 link	c.302G>A	p.Ser101Asn	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.302G>A	p.Ser101Asn	missense_variant	Exon 2 of 2	1	NM_001011551.3	ENSP00000304364.5		Q96EU7
C1GALT1C1	ENST00000371313.2 link	c.302G>A	p.Ser101Asn	missense_variant	Exon 3 of 3	1		ENSP00000360363.2		Q96EU7

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

535

AN:

111834

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

139

AN XY:

34008

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.000829

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00814

Gnomad OTH

AF:

0.00467

GnomAD3 exomes

AF:

0.00422

AC:

771

AN:

182742

Hom.:

AF XY:

0.00428

AC XY:

288

AN XY:

67270

show subpopulations

Gnomad AFR exome

AF:

0.000838

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.000942

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000316

Gnomad FIN exome

AF:

0.00100

Gnomad NFE exome

AF:

0.00800

Gnomad OTH exome

AF:

0.00422

GnomAD4 exome

AF:

0.00765

AC:

8402

AN:

1097921

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

2615

AN XY:

363309

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000259

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.00933

Gnomad4 OTH exome

AF:

0.00712

GnomAD4 genome

AF:

0.00478

AC:

535

AN:

111889

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

139

AN XY:

34073

show subpopulations

Gnomad4 AFR

AF:

0.000940

Gnomad4 AMR

AF:

0.00334

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000371

Gnomad4 FIN

AF:

0.000829

Gnomad4 NFE

AF:

0.00814

Gnomad4 OTH

AF:

0.00461

Alfa

AF:

0.00708

Hom.:

295

Bravo

AF:

0.00484

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00847

AC:

ExAC

AF:

0.00426

AC:

517

EpiCase

AF:

0.00774

EpiControl

AF:

0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Polyagglutinable erythrocyte syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

C1GALT1C1-related disorder

Benign:1

Aug 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Pathogenic

0.87

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

D;D

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.5

M;M

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.19

Sift

Benign

0.048

D;D

Sift4G

Uncertain

0.059

T;T

Polyphen

0.0080

B;B

Vest4

0.18

MVP

0.57

MPC

0.28

ClinPred

0.066

GERP RS

5.3

Varity_R

0.72

gMVP

0.90

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