7-7238519-C-G

Variant summary

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

The NM_020156.5(C1GALT1):ā€‹c.485C>Gā€‹(p.Ala162Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

C1GALT1
NM_020156.5 missense

Scores

2
14
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16
Variant links:
Genes affected
C1GALT1 (HGNC:24337): (core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1) The protein encoded by this gene generates the common core 1 O-glycan structure, Gal-beta-1-3GalNAc-R, by the transfer of Gal from UDP-Gal to GalNAc-alpha-1-R. Core 1 is a precursor for many extended mucin-type O-glycans on cell surface and secreted glycoproteins. Studies in mice suggest that this gene plays a key role in thrombopoiesis and kidney homeostasis.[provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C1GALT1NM_020156.5 linkc.485C>G p.Ala162Gly missense_variant 3/4 ENST00000436587.7 NP_064541.1 Q9NS00-1A0A024RA32

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C1GALT1ENST00000436587.7 linkc.485C>G p.Ala162Gly missense_variant 3/45 NM_020156.5 ENSP00000389176.2 Q9NS00-1
C1GALT1ENST00000223122.4 linkc.485C>G p.Ala162Gly missense_variant 2/31 ENSP00000223122.2 Q9NS00-1
C1GALT1ENST00000402468.3 linkc.485C>G p.Ala162Gly missense_variant 2/21 ENSP00000384550.3 Q9NS00-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461810
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727194
show subpopulations
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 19, 2024The c.485C>G (p.A162G) alteration is located in exon 3 (coding exon 2) of the C1GALT1 gene. This alteration results from a C to G substitution at nucleotide position 485, causing the alanine (A) at amino acid position 162 to be replaced by a glycine (G). 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
Benign
0.21
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;D;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;.;D
M_CAP
Benign
0.044
D
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Uncertain
2.5
M;M;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.5
D;D;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.027
D;D;D
Sift4G
Uncertain
0.019
D;D;D
Polyphen
0.57
P;P;D
Vest4
0.77
MutPred
0.58
Loss of stability (P = 0.078);Loss of stability (P = 0.078);Loss of stability (P = 0.078);
MVP
0.43
MPC
0.49
ClinPred
0.98
D
GERP RS
5.4
Varity_R
0.49
gMVP
0.67

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: chr7-7278150; API