7-7238519-C-G

Variant names:

• chr7-7238519-C-G
• NM_020156.5:c.485C>G

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

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]

ACMG classification

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 rank	MANE	Protein	UniProt
C1GALT1	NM_020156.5	c.485C>G	p.Ala162Gly	missense_variant	Exon 3 of 4	ENST00000436587.7	NP_064541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1GALT1	ENST00000436587.7	c.485C>G	p.Ala162Gly	missense_variant	Exon 3 of 4	5	NM_020156.5	ENSP00000389176.2
C1GALT1	ENST00000223122.4	c.485C>G	p.Ala162Gly	missense_variant	Exon 2 of 3	1		ENSP00000223122.2
C1GALT1	ENST00000402468.3	c.485C>G	p.Ala162Gly	missense_variant	Exon 2 of 2	1		ENSP00000384550.3
C1GALT1	ENST00000429911.5	c.*91C>G		downstream_gene_variant		5		ENSP00000407666.1

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

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

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	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;