7-7238632-C-T

Position:

• chr7-7238632-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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/exons	MANE	Protein	UniProt
C1GALT1	NM_020156.5	c.598C>T	p.Pro200Ser	missense_variant	3/4	ENST00000436587.7	NP_064541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1GALT1	ENST00000436587.7	c.598C>T	p.Pro200Ser	missense_variant	3/4	5	NM_020156.5	ENSP00000389176.2
C1GALT1	ENST00000223122.4	c.598C>T	p.Pro200Ser	missense_variant	2/3	1		ENSP00000223122.2
C1GALT1	ENST00000402468.3	c.598C>T	p.Pro200Ser	missense_variant	2/2	1		ENSP00000384550.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2024

The c.598C>T (p.P200S) alteration is located in exon 3 (coding exon 2) of the C1GALT1 gene. This alteration results from a C to T substitution at nucleotide position 598, causing the proline (P) at amino acid position 200 to be replaced by a serine (S). 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	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;D;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-7.2	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.59	P;P;P
Vest4		0.73
MutPred		0.37		Gain of MoRF binding (P = 0.0478);Gain of MoRF binding (P = 0.0478);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

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: chr7-7278263;