X-120626865-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.70

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]

ACMG classification

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 GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1GALT1C1	NM_001011551.3	c.302G>A	p.Ser101Asn	missense_variant	2/2	ENST00000304661.6
C1GALT1C1	NM_152692.5	c.302G>A	p.Ser101Asn	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1C1	ENST00000304661.6	c.302G>A	p.Ser101Asn	missense_variant	2/2	1	NM_001011551.3	P1
C1GALT1C1	ENST00000371313.2	c.302G>A	p.Ser101Asn	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 535 AN: 111834 Hom.: 2 Cov.: 23 AF XY: 0.00409 AC XY: 139 AN XY: 34008

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.: 1 AF XY: 0.00428 AC XY: 288 AN XY: 67270

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.: 29 Cov.: 32 AF XY: 0.00720 AC XY: 2615 AN XY: 363309

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.: 2 Cov.: 23 AF XY: 0.00408 AC XY: 139 AN XY: 34073

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: 39

ALSPAC AF: 0.0104 AC: 30

ESP6500AA AF: 0.000782 AC: 3

ESP6500EA AF: 0.00847 AC: 57

ExAC AF: 0.00426 AC: 517

EpiCase AF: 0.00774

EpiControl AF: 0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Polyagglutinable erythrocyte syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

C1GALT1C1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 07, 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D;D
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0088	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.5	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
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	T
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

Other links and lift over

dbSNP: rs149340486; hg19: chrX-119760720;