3-195156489-C-A

Variant names:

• chr3-195156489-C-A
• rs779805397
• NM_152531.5:c.745G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152531.5(XXYLT1):​c.745G>T​(p.Ala249Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A249T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: XXYLT1 NM_152531.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99
• Publications: 1 publications found

Genes affected

XXYLT1 (HGNC:26639): (xyloside xylosyltransferase 1) Enables magnesium ion binding activity; manganese ion binding activity; and xylosyl alpha-1,3-xylosyltransferase activity. Involved in O-glycan processing. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17761672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152531.5. 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
	XXYLT1	NM_152531.5	MANE Select	c.745G>T	p.Ala249Ser	missense	Exon 3 of 4	NP_689744.3
	XXYLT1	NM_001308069.2		c.307G>T	p.Ala103Ser	missense	Exon 3 of 4	NP_001294998.1	A0A140T9D0
	XXYLT1	NM_001410854.1		c.136G>T	p.Ala46Ser	missense	Exon 2 of 3	NP_001397783.1	Q8NBI6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XXYLT1	ENST00000310380.11	TSL:1 MANE Select	c.745G>T	p.Ala249Ser	missense	Exon 3 of 4	ENSP00000309640.6	Q8NBI6-1
	XXYLT1	ENST00000429994.5	TSL:3	c.307G>T	p.Ala103Ser	missense	Exon 3 of 4	ENSP00000399422.1	A0A140T9D0
	XXYLT1	ENST00000437101.5	TSL:2	c.136G>T	p.Ala46Ser	missense	Exon 4 of 5	ENSP00000409865.1	Q8NBI6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249482 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461826 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.057
Sift	Benign	0.33	T
Sift4G	Benign	0.42	T
Polyphen		0.12	B
Vest4		0.47
MutPred		0.51		Loss of helix (P = 0.0626)
MVP		0.030
MPC		0.64
ClinPred		0.30	T
GERP RS		4.6
Varity_R		0.031
gMVP		0.64
Mutation Taster		=64/36	polymorphism

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: rs779805397; hg19: chr3-194877218;