NM_001080393.2:c.528A>G

Variant names:

• chr3-72922263-A-G
• rs61741329
• NM_001080393.2:c.528A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080393.2(GXYLT2):​c.528A>G​(p.Thr176Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,613,666 control chromosomes in the GnomAD database, including 430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (206 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (224 hom.)
• Consequence: GXYLT2 NM_001080393.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.398
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-72922263-A-G is Benign according to our data. Variant chr3-72922263-A-G is described in ClinVar as Benign. ClinVar VariationId is 767917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.398 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

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.528A>G	p.Thr176Thr	synonymous	Exon 3 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.716A>G		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.528A>G	p.Thr176Thr	synonymous	Exon 3 of 7	ENSP00000374268.4	A0PJZ3
	GXYLT2	ENST00000498315.1	TSL:2	c.150A>G	p.Thr50Thr	synonymous	Exon 2 of 3	ENSP00000417239.1	C9J3Q6
	ENSG00000299702	ENST00000765725.1		n.128+10672T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4421 AN: 152076 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.00731 AC: 1820 AN: 249110 AF XY: 0.00536

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00630

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00310 AC: 4536 AN: 1461472 Hom.: 224 Cov.: 30 AF XY: 0.00271 AC XY: 1967 AN XY: 727062

African (AFR) AF: 0.107 AC: 3562 AN: 33430

American (AMR) AF: 0.00725 AC: 324 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86236

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53400

Middle Eastern (MID) AF: 0.00642 AC: 37 AN: 5766

European-Non Finnish (NFE) AF: 0.000117 AC: 130 AN: 1111748

Other (OTH) AF: 0.00755 AC: 456 AN: 60360

GnomAD4 genome AF: 0.0291 AC: 4434 AN: 152194 Hom.: 206 Cov.: 32 AF XY: 0.0281 AC XY: 2089 AN XY: 74436

African (AFR) AF: 0.0992 AC: 4115 AN: 41494

American (AMR) AF: 0.0161 AC: 246 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68018

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0132 Hom.: 69

Bravo AF: 0.0335

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		-0.40
Mutation Taster		=98/2	polymorphism (auto)

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

dbSNP: rs61741329; hg19: chr3-72971414;