chrX-120626739-G-A

Position:

chrX-120626739-G-A

Variant summary

Our verdict is Benign. Variant got -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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1GALT1C1	NM_001011551.3 linkuse as main transcript	c.428C>T	p.Ala143Val	missense_variant	2/2	ENST00000304661.6
C1GALT1C1	NM_152692.5 linkuse as main transcript	c.428C>T	p.Ala143Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1C1	ENST00000304661.6 linkuse as main transcript	c.428C>T	p.Ala143Val	missense_variant	2/2	1	NM_001011551.3	P1
C1GALT1C1	ENST00000371313.2 linkuse as main transcript	c.428C>T	p.Ala143Val	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

2256

AN:

111891

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

758

AN XY:

34055

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

GnomAD3 exomes

AF:

0.0223

AC:

4084

AN:

182776

Hom.:

AF XY:

0.0227

AC XY:

1532

AN XY:

67364

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 SAS exome

AF:

0.00747

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

Gnomad4 AMR exome

AF:

0.00723

Gnomad4 ASJ exome

AF:

0.0125

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00772

Gnomad4 FIN exome

AF:

0.0880

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0213

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

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00554

Gnomad4 FIN

AF:

0.0973

Gnomad4 NFE

AF:

0.0261

Gnomad4 OTH

AF:

0.0144

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

MutationTaster

Benign

4.6e-8

P;P

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

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