X-120626739-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001011551.3(C1GALT1C1):c.428C>T(p.Ala143Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,209,784 control chromosomes in the GnomAD database, including 365 homozygotes. There are 9,445 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (23 hom., 757 hem., cov: 23)
  • Exomes 𝑓: 0.024 (342 hom. 8688 hem.)
• Consequence: C1GALT1C1 NM_001011551.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.67

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009571731).
• BP6: Variant X-120626739-G-A is Benign according to our data. Variant chrX-120626739-G-A is described in ClinVar as [Benign]. Clinvar id is 460285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0201 (2255/111944) while in subpopulation NFE AF= 0.0261 (1390/53196). AF 95% confidence interval is 0.025. There are 23 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1GALT1C1	NM_001011551.3	c.428C>T	p.Ala143Val	missense_variant	2/2	ENST00000304661.6
C1GALT1C1	NM_152692.5	c.428C>T	p.Ala143Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1C1	ENST00000304661.6	c.428C>T	p.Ala143Val	missense_variant	2/2	1	NM_001011551.3	P1
C1GALT1C1	ENST00000371313.2	c.428C>T	p.Ala143Val	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2256 AN: 111891 Hom.: 23 Cov.: 23 AF XY: 0.0223 AC XY: 758 AN XY: 34055

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00875

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00552

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0146

GnomAD3 exomes AF: 0.0223 AC: 4084 AN: 182776 Hom.: 80 AF XY: 0.0227 AC XY: 1532 AN XY: 67364

Gnomad AFR exome AF: 0.00337

Gnomad AMR exome AF: 0.00693

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00747

Gnomad FIN exome AF: 0.0956

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0228

GnomAD4 exome AF: 0.0243 AC: 26698 AN: 1097840 Hom.: 342 Cov.: 31 AF XY: 0.0239 AC XY: 8688 AN XY: 363234

Gnomad4 AFR exome AF: 0.00265

Gnomad4 AMR exome AF: 0.00723

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.0000994

Gnomad4 SAS exome AF: 0.00772

Gnomad4 FIN exome AF: 0.0880

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0201 AC: 2255 AN: 111944 Hom.: 23 Cov.: 23 AF XY: 0.0222 AC XY: 757 AN XY: 34118

Gnomad4 AFR AF: 0.00288

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00554

Gnomad4 FIN AF: 0.0973

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0144

Alfa AF: 0.0252 Hom.: 427

Bravo AF: 0.0142

TwinsUK AF: 0.0256 AC: 95

ALSPAC AF: 0.0280 AC: 81

ESP6500AA AF: 0.00469 AC: 18

ESP6500EA AF: 0.0248 AC: 167

ExAC AF: 0.0216 AC: 2623

EpiCase AF: 0.0228

EpiControl AF: 0.0196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polyagglutinable erythrocyte syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;D
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0096	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	4.6e-8	P;P
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		0.16	B;B
Vest4		0.20
MPC		0.59
ClinPred		0.019	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.93

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: rs45557031; hg19: chrX-119760594;