chr7-7238632-C-T

Variant names:

• chr7-7238632-C-T
• NM_020156.5:c.598C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020156.5(C1GALT1):​c.598C>T​(p.Pro200Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1GALT1 NM_020156.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020156.5. 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
	C1GALT1	NM_020156.5	MANE Select	c.598C>T	p.Pro200Ser	missense	Exon 3 of 4	NP_064541.1	Q9NS00-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1GALT1	ENST00000436587.7	TSL:5 MANE Select	c.598C>T	p.Pro200Ser	missense	Exon 3 of 4	ENSP00000389176.2	Q9NS00-1
	C1GALT1	ENST00000223122.4	TSL:1	c.598C>T	p.Pro200Ser	missense	Exon 2 of 3	ENSP00000223122.2	Q9NS00-1
	C1GALT1	ENST00000402468.3	TSL:1	c.598C>T	p.Pro200Ser	missense	Exon 2 of 2	ENSP00000384550.3	Q9NS00-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.012	D
Polyphen		0.59	P
Vest4		0.73
MutPred		0.37		Gain of MoRF binding (P = 0.0478)
MVP		0.28
MPC		0.48
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.68
Mutation Taster		=34/66	disease causing

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

hg19: chr7-7278263;