7-7238375-G-T

Variant summary

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

The NM_020156.5(C1GALT1):c.341G>T(p.Arg114Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R114H) has been classified 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: 1.70

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	UniProt
C1GALT1	NM_020156.5	c.341G>T	p.Arg114Leu	missense_variant	3/4	ENST00000436587.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1	ENST00000436587.7	c.341G>T	p.Arg114Leu	missense_variant	3/4	5	NM_020156.5	P1
C1GALT1	ENST00000223122.4	c.341G>T	p.Arg114Leu	missense_variant	2/3	1		P1
C1GALT1	ENST00000402468.3	c.341G>T	p.Arg114Leu	missense_variant	2/2	1
C1GALT1	ENST00000429911.5	c.341G>T	p.Arg114Leu	missense_variant	4/4	5

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

May 18, 2022

The c.341G>T (p.R114L) alteration is located in exon 3 (coding exon 2) of the C1GALT1 gene. This alteration results from a G to T substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a leucine (L). 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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.0	D;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.018	D;D;D;D
Sift4G	Benign	0.099	T;D;D;D
Polyphen		0.93, 0.63	.;P;P;P
Vest4		0.68, 0.68, 0.60
MutPred		0.62		Loss of MoRF binding (P = 0.0434);Loss of MoRF binding (P = 0.0434);Loss of MoRF binding (P = 0.0434);Loss of MoRF binding (P = 0.0434);
MVP		0.50
MPC		0.35
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.61
gMVP		0.81

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: chr7-7278006;