Variant 7-7238519-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020156.5(C1GALT1):c.485C>G(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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

C1GALT1
NM_020156.5 missense

Scores

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]

C1GALT1 links:

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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
C1GALT1	NM_020156.5 link	c.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	UniProt
C1GALT1	ENST00000436587.7 link	c.485C>G	p.Ala162Gly	missense_variant	3/4	5	NM_020156.5	ENSP00000389176.2	Q9NS00-1
C1GALT1	ENST00000223122.4 link	c.485C>G	p.Ala162Gly	missense_variant	2/3	1		ENSP00000223122.2	Q9NS00-1
C1GALT1	ENST00000402468.3 link	c.485C>G	p.Ala162Gly	missense_variant	2/2	1		ENSP00000384550.3	Q9NS00-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

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.:

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 submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The 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

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;D;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Uncertain

0.67

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over