NM_001011551.3:c.597C>G

Variant names:

• chrX-120626570-G-C
• rs755698477
• NM_001011551.3:c.597C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 15/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.317
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028200388).
• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

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.597C>G	p.Ser199Arg	missense	Exon 2 of 2	NP_001011551.1	Q96EU7
	C1GALT1C1	NM_152692.5		c.597C>G	p.Ser199Arg	missense	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.597C>G	p.Ser199Arg	missense	Exon 2 of 2	ENSP00000304364.5	Q96EU7
	C1GALT1C1	ENST00000371313.2	TSL:1	c.597C>G	p.Ser199Arg	missense	Exon 3 of 3	ENSP00000360363.2	Q96EU7
	C1GALT1C1	ENST00000899457.1		c.597C>G	p.Ser199Arg	missense	Exon 2 of 2	ENSP00000569516.1

Frequencies

GnomAD3 genomes AF: 0.0000801 AC: 9 AN: 112301 Hom.: 0 Cov.: 24

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

GnomAD2 exomes AF: 0.0000437 AC: 8 AN: 183168 AF XY: 0.0000739

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097260 Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 6 AN XY: 362684

African (AFR) AF: 0.0000379 AC: 1 AN: 26381

American (AMR) AF: 0.00 AC: 0 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19371

East Asian (EAS) AF: 0.0000994 AC: 3 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 841310

Other (OTH) AF: 0.000109 AC: 5 AN: 46066

GnomAD4 genome AF: 0.0000801 AC: 9 AN: 112357 Hom.: 0 Cov.: 24 AF XY: 0.000116 AC XY: 4 AN XY: 34545

African (AFR) AF: 0.000226 AC: 7 AN: 30982

American (AMR) AF: 0.00 AC: 0 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.000279 AC: 1 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53272

Other (OTH) AF: 0.000655 AC: 1 AN: 1527

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.87
DEOGEN2	Benign	0.064	T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	N
PhyloP100		0.32
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.24
Sift	Benign	0.64	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.30		Loss of phosphorylation at S199 (P = 0.0432)
MVP		0.84
MPC		0.31
ClinPred		0.0085	T
GERP RS		3.4
Varity_R		0.20
gMVP		0.37
Mutation Taster		=95/5	polymorphism

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: rs755698477; hg19: chrX-119760425;