3-38376154-A-G

Position:

• chr3-38376154-A-G

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.1042A>G​(p.Asn348Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,614,086 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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.

• Frequency:
  • Genomes: 𝑓 0.026 (170 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (145 hom.)
• Consequence: XYLB NM_005108.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.95

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=0.002586186).
• BP6: Variant 3-38376154-A-G is Benign according to our data. Variant chr3-38376154-A-G is described in ClinVar as [Benign]. Clinvar id is 775858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLB	NM_005108.4	c.1042A>G	p.Asn348Asp	missense_variant	13/19	ENST00000207870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLB	ENST00000207870.8	c.1042A>G	p.Asn348Asp	missense_variant	13/19	1	NM_005108.4	P1
XYLB	ENST00000650590.1	c.961A>G	p.Asn321Asp	missense_variant	12/18
XYLB	ENST00000424034.5	c.*705A>G		3_prime_UTR_variant, NMD_transcript_variant	11/17	2
XYLB	ENST00000649234.1	c.*277A>G		3_prime_UTR_variant, NMD_transcript_variant	14/20

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4032 AN: 152160 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0310

GnomAD3 exomes AF: 0.00733 AC: 1844 AN: 251466 Hom.: 64 AF XY: 0.00562 AC XY: 764 AN XY: 135910

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.00809

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000738

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00310 AC: 4537 AN: 1461808 Hom.: 145 Cov.: 30 AF XY: 0.00280 AC XY: 2039 AN XY: 727206

Gnomad4 AFR exome AF: 0.0925

Gnomad4 AMR exome AF: 0.00897

Gnomad4 ASJ exome AF: 0.000612

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000487

Gnomad4 OTH exome AF: 0.00687

GnomAD4 genome AF: 0.0265 AC: 4035 AN: 152278 Hom.: 170 Cov.: 32 AF XY: 0.0254 AC XY: 1888 AN XY: 74476

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.00591 Hom.: 46

Bravo AF: 0.0314

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0837 AC: 369

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00865 AC: 1050

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000830

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	0.050
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.0
DANN	Benign	0.15
DEOGEN2	Benign	0.0089	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.40	T;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.91	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.4	N;.
REVEL	Benign	0.032
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.0	B;.
Vest4		0.073
MVP		0.030
MPC		0.11
ClinPred		0.0030	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs2234622; hg19: chr3-38417645;