rs200973382

Variant names:

Variant summary

Our verdict is Benign. Variant got -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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 -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 id is 2051173.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1GALT1C1	NM_001011551.3 link	c.666G>C	p.Gln222His	missense_variant	Exon 2 of 2	ENST00000304661.6	NP_001011551.1	Q96EU7
C1GALT1C1	NM_152692.5 link	c.666G>C	p.Gln222His	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.666G>C	p.Gln222His	missense_variant	Exon 2 of 2	1	NM_001011551.3	ENSP00000304364.5		Q96EU7
C1GALT1C1	ENST00000371313.2 link	c.666G>C	p.Gln222His	missense_variant	Exon 3 of 3	1		ENSP00000360363.2		Q96EU7

Frequencies

GnomAD3 genomes

AF:

0.000222

AC:

AN:

112692

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

34834

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

GnomAD3 exomes

AF:

0.000393

AC:

AN:

183344

Hom.:

AF XY:

0.000560

AC XY:

AN XY:

67820

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 SAS exome

AF:

0.00157

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.000325

GnomAD4 genome

AF:

0.000222

AC:

AN:

112747

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

34899

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00287

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000319

Gnomad4 OTH

AF:

0.00

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

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Polyagglutinable erythrocyte syndrome

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

C1GALT1C1-related disorder

Benign:1

Feb 23, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

0.73

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Uncertain

0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

M;M

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.32

B;B

Vest4

0.28

MutPred

0.67

Gain of sheet (P = 0.0827);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

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