Variant 3-38376154-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.95

Variant links:

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]

XYLB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 linkuse as main transcript	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 linkuse as main transcript	c.1042A>G	p.Asn348Asp	missense_variant	13/19	1	NM_005108.4	P1	O75191-1
XYLB	ENST00000650590.1 linkuse as main transcript	c.961A>G	p.Asn321Asp	missense_variant	12/18
XYLB	ENST00000424034.5 linkuse as main transcript	c.*705A>G		3_prime_UTR_variant, NMD_transcript_variant	11/17	2
XYLB	ENST00000649234.1 linkuse as main transcript	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.:

show subpopulations

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.:

AF XY:

0.00562

AC XY:

764

AN XY:

135910

show subpopulations

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.:

AF XY:

0.00280

AC XY:

2039

AN XY:

727206

show subpopulations

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.:

AF XY:

0.0254

AC XY:

1888

AN XY:

74476

show subpopulations

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.:

Bravo

AF:

0.0314

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0837

AC:

369

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00865

AC:

1050

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.72

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

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.91

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over