rs200344844

Variant names:

• chr3-72922207-C-A
• rs200344844
• NM_001080393.2:c.472C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-72922207-C-A
• chr3-72922207-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080393.2(GXYLT2):​c.472C>A​(p.Arg158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 0 publications found

Genes affected

GXYLT2 (HGNC:33383): (glucoside xylosyltransferase 2) The protein encoded by this gene is a xylosyltransferase that elongates O-linked glucose bound to epidermal growth factor (EGF) repeats. The encoded protein catalyzes the addition of xylose to the O-glucose-modified residues of EGF repeats of Notch proteins. [provided by RefSeq, Sep 2016]

ENSG00000299702 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05576858).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080393.2. 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
	GXYLT2	NM_001080393.2	MANE Select	c.472C>A	p.Arg158Ser	missense	Exon 3 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.660C>A		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GXYLT2	ENST00000389617.9	TSL:5 MANE Select	c.472C>A	p.Arg158Ser	missense	Exon 3 of 7	ENSP00000374268.4	A0PJZ3
	GXYLT2	ENST00000498315.1	TSL:2	c.94C>A	p.Arg32Ser	missense	Exon 2 of 3	ENSP00000417239.1	C9J3Q6
	ENSG00000299702	ENST00000765725.1		n.128+10728G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459162 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725834

African (AFR) AF: 0.00 AC: 0 AN: 33294

American (AMR) AF: 0.00 AC: 0 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 85654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110846

Other (OTH) AF: 0.00 AC: 0 AN: 60276

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		1.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.078
Sift	Benign	0.82	T
Sift4G	Benign	0.72	T
Polyphen		0.065	B
Vest4		0.30
MutPred		0.35		Gain of disorder (P = 0.0502)
MVP		0.33
MPC		0.18
ClinPred		0.22	T
GERP RS		5.8
Varity_R		0.14
gMVP		0.34
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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

dbSNP: rs200344844; hg19: chr3-72971358;