Genetic Variant NM_001011551.3:c.515C>T (chrX-120626652-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001011551.3(C1GALT1C1):c.515C>T(p.Thr172Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000166 in 1,207,291 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2921372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1GALT1C1	NM_001011551.3 link	c.515C>T	p.Thr172Ile	missense_variant	Exon 2 of 2	ENST00000304661.6	NP_001011551.1	Q96EU7
C1GALT1C1	NM_152692.5 link	c.515C>T	p.Thr172Ile	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.515C>T	p.Thr172Ile	missense_variant	Exon 2 of 2	1	NM_001011551.3	ENSP00000304364.5		Q96EU7
C1GALT1C1	ENST00000371313.2 link	c.515C>T	p.Thr172Ile	missense_variant	Exon 3 of 3	1		ENSP00000360363.2		Q96EU7

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34170

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.13e-7

AC:

AN:

1095301

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361057

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34170

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.12

Sift

Benign

0.047

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.37

B;B

Vest4

0.43

MutPred

0.52

Loss of phosphorylation at T172 (P = 0.0612);Loss of phosphorylation at T172 (P = 0.0612);

MVP

0.65

MPC

0.56

ClinPred

0.94

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.66

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over