3-38365626-G-A

Position:

• chr3-38365626-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005108.4(XYLB):​c.397G>A​(p.Asp133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,612,978 control chromosomes in the GnomAD database, including 388 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D133G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.031 (219 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (169 hom.)
• Consequence: XYLB NM_005108.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.702

Genes affected

XYLB (HGNC:12839): (xylulokinase) The protein encoded by this gene shares 22% sequence identity with Hemophilus influenzae xylulokinase, and even higher identity to other gene products in C.elegans (45%) and yeast (31-35%), which are thought to belong to a family of enzymes that include fucokinase, gluconokinase, glycerokinase and xylulokinase. These proteins play important roles in energy metabolism. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019536912).
• BP6: Variant 3-38365626-G-A is Benign according to our data. Variant chr3-38365626-G-A is described in ClinVar as [Benign]. Clinvar id is 775857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLB	NM_005108.4	c.397G>A	p.Asp133Asn	missense_variant	6/19	ENST00000207870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLB	ENST00000207870.8	c.397G>A	p.Asp133Asn	missense_variant	6/19	1	NM_005108.4	P1
XYLB	ENST00000650590.1	c.316G>A	p.Asp106Asn	missense_variant	5/18
XYLB	ENST00000649234.1	c.397G>A	p.Asp133Asn	missense_variant, NMD_transcript_variant	6/20
XYLB	ENST00000424034.5	c.*60G>A		3_prime_UTR_variant, NMD_transcript_variant	4/17	2

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4656 AN: 152196 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.0321

GnomAD3 exomes AF: 0.00869 AC: 2176 AN: 250314 Hom.: 90 AF XY: 0.00677 AC XY: 916 AN XY: 135236

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00838

Gnomad ASJ exome AF: 0.00797

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000885

Gnomad OTH exome AF: 0.00754

GnomAD4 exome AF: 0.00364 AC: 5316 AN: 1460664 Hom.: 169 Cov.: 32 AF XY: 0.00331 AC XY: 2403 AN XY: 726440

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.00963

Gnomad4 ASJ exome AF: 0.00896

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000584

Gnomad4 OTH exome AF: 0.00870

GnomAD4 genome AF: 0.0306 AC: 4663 AN: 152314 Hom.: 219 Cov.: 32 AF XY: 0.0294 AC XY: 2189 AN XY: 74478

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000852

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.00797 Hom.: 86

Bravo AF: 0.0357

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0958 AC: 422

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00988 AC: 1200

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.90	D;D
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.47	N;.
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.076
Sift	Benign	0.28	T;.
Sift4G	Benign	0.60	T;.
Polyphen		0.0010	B;.
Vest4		0.17
MVP		0.14
MPC		0.093
ClinPred		0.0091	T
GERP RS		1.4
Varity_R		0.27
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2234610; hg19: chr3-38407117;