X-120626418-G-A

Variant names:

• chrX-120626418-G-A
• NM_001011551.3:c.749C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001011551.3(C1GALT1C1):​c.749C>T​(p.Ser250Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: C1GALT1C1 NM_001011551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99

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 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=0.3753538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1GALT1C1	NM_001011551.3	c.749C>T	p.Ser250Phe	missense_variant	Exon 2 of 2	ENST00000304661.6	NP_001011551.1
C1GALT1C1	NM_152692.5	c.749C>T	p.Ser250Phe	missense_variant	Exon 3 of 3		NP_689905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1GALT1C1	ENST00000304661.6	c.749C>T	p.Ser250Phe	missense_variant	Exon 2 of 2	1	NM_001011551.3	ENSP00000304364.5
C1GALT1C1	ENST00000371313.2	c.749C>T	p.Ser250Phe	missense_variant	Exon 3 of 3	1		ENSP00000360363.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.749C>T (p.S250F) alteration is located in exon 3 (coding exon 1) of the C1GALT1C1 gene. This alteration results from a C to T substitution at nucleotide position 749, causing the serine (S) at amino acid position 250 to be replaced by a phenylalanine (F). 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.21
Sift	Benign	0.049	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.81	P;P
Vest4		0.43
MutPred		0.51		Gain of methylation at K249 (P = 0.0272);Gain of methylation at K249 (P = 0.0272);
MVP		0.77
MPC		0.76
ClinPred		0.71	D
GERP RS		5.5
Varity_R		0.26
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-119760273;