12-42129837-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173601.2(GXYLT1):c.236C>G(p.Ser79Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GXYLT1 NM_173601.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.35

Genes affected

GXYLT1 (HGNC:27482): (glucoside xylosyltransferase 1) GXYLT1 is a xylosyltransferase (EC 2.4.2.-) that adds the first xylose to O-glucose-modified residues in the epidermal growth factor (EGF; MIM 131530) repeats of proteins such as NOTCH1 (MIM 190198) (Sethi et al., 2010 [PubMed 19940119]).[supplied by OMIM, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1313214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GXYLT1	NM_173601.2	c.236C>G	p.Ser79Cys	missense_variant	2/8	ENST00000398675.8
GXYLT1	XM_017019211.1	c.-293C>G		5_prime_UTR_variant	1/8
GXYLT1	NM_001099650.2	c.222-10666C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GXYLT1	ENST00000398675.8	c.236C>G	p.Ser79Cys	missense_variant	2/8	1	NM_173601.2	P4
GXYLT1	ENST00000280876.6	c.222-10666C>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Feb 21, 2024

The c.236C>G (p.S79C) alteration is located in exon 2 (coding exon 2) of the GXYLT1 gene. This alteration results from a C to G substitution at nucleotide position 236, causing the serine (S) at amino acid position 79 to be replaced by a cysteine (C). 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	0.16
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.0056
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.56	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0010	B
Vest4		0.29
MutPred		0.39		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.068
MPC		0.51
ClinPred		0.80	D
GERP RS		3.4
Varity_R		0.17
gMVP		0.70

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: chr12-42523639; COSMIC: COSV55142340;