rs752289824

Variant names:

• chrX-120626561-A-G
• rs752289824
• NM_001011551.3:c.606T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-120626561-A-G
• chrX-120626561-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001011551.3(C1GALT1C1):​c.606T>C​(p.Asn202Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,807 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: C1GALT1C1 NM_001011551.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.213 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011551.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1GALT1C1	NM_001011551.3	MANE Select	c.606T>C	p.Asn202Asn	synonymous	Exon 2 of 2	NP_001011551.1	Q96EU7
	C1GALT1C1	NM_152692.5		c.606T>C	p.Asn202Asn	synonymous	Exon 3 of 3	NP_689905.1	Q96EU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1GALT1C1	ENST00000304661.6	TSL:1 MANE Select	c.606T>C	p.Asn202Asn	synonymous	Exon 2 of 2	ENSP00000304364.5	Q96EU7
	C1GALT1C1	ENST00000371313.2	TSL:1	c.606T>C	p.Asn202Asn	synonymous	Exon 3 of 3	ENSP00000360363.2	Q96EU7
	C1GALT1C1	ENST00000899457.1		c.606T>C	p.Asn202Asn	synonymous	Exon 2 of 2	ENSP00000569516.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097807 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363197

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40509

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841775

Other (OTH) AF: 0.00 AC: 0 AN: 46083

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.56
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs752289824; hg19: chrX-119760416;