X-120626570-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001011551.3(C1GALT1C1):c.597C>G(p.Ser199Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,209,617 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 6 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028200388).

BS2

High Hemizygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1GALT1C1	NM_001011551.3 linkuse as main transcript	c.597C>G	p.Ser199Arg	missense_variant	2/2	ENST00000304661.6
C1GALT1C1	NM_152692.5 linkuse as main transcript	c.597C>G	p.Ser199Arg	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1C1	ENST00000304661.6 linkuse as main transcript	c.597C>G	p.Ser199Arg	missense_variant	2/2	1	NM_001011551.3	P1
C1GALT1C1	ENST00000371313.2 linkuse as main transcript	c.597C>G	p.Ser199Arg	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000801

AC:

AN:

112301

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34479

show subpopulations

Gnomad AFR

AF:

0.000226

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000663

GnomAD3 exomes

AF:

0.0000437

AC:

AN:

183168

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

67658

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000361

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1097260

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

362684

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000801

AC:

AN:

112357

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34545

show subpopulations

Gnomad4 AFR

AF:

0.000226

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000655

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.597C>G (p.S199R) alteration is located in exon 3 (coding exon 1) of the C1GALT1C1 gene. This alteration results from a C to G substitution at nucleotide position 597, causing the serine (S) at amino acid position 199 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.064

T;T

FATHMM_MKL

Benign

0.24

M_CAP

Benign

0.0063

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.13

N;N

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.24

Sift

Benign

0.64

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

B;B

Vest4

0.065

MutPred

0.30

Loss of phosphorylation at S199 (P = 0.0432);Loss of phosphorylation at S199 (P = 0.0432);

MVP

0.84

MPC

0.31

ClinPred

0.0085

GERP RS

3.4

Varity_R

0.20

gMVP

0.37

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