chrX-120626719-T-G

Variant names:

• chrX-120626719-T-G
• rs777518677
• NM_001011551.3:c.448A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001011551.3(C1GALT1C1):​c.448A>C​(p.Ile150Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,939 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: C1GALT1C1 NM_001011551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25004697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1GALT1C1	NM_001011551.3	c.448A>C	p.Ile150Leu	missense_variant	Exon 2 of 2	ENST00000304661.6	NP_001011551.1
C1GALT1C1	NM_152692.5	c.448A>C	p.Ile150Leu	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.448A>C	p.Ile150Leu	missense_variant	Exon 2 of 2	1	NM_001011551.3	ENSP00000304364.5
C1GALT1C1	ENST00000371313.2	c.448A>C	p.Ile150Leu	missense_variant	Exon 3 of 3	1		ENSP00000360363.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000547 AC: 1 AN: 182963 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67507

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097939 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363315

Gnomad4 AFR exome AF: 0.00

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.044	D;D
Polyphen		0.014	B;B
Vest4		0.32
MutPred		0.68		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.70
MPC		0.37
ClinPred		0.24	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.83

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: rs777518677; hg19: chrX-119760574;