Variant 19-7627389-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020196.3(XAB2):c.376G>A(p.Val126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,607,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

XAB2
NM_020196.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

XAB2 (HGNC:14089): (XPA binding protein 2) Involved in mRNA splicing, via spliceosome; transcription, DNA-templated; and transcription-coupled nucleotide-excision repair. Located in nucleoplasm. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

XAB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028428853).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XAB2	NM_020196.3 linkuse as main transcript	c.376G>A	p.Val126Ile	missense_variant	4/19	ENST00000358368.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XAB2	ENST00000358368.5 linkuse as main transcript	c.376G>A	p.Val126Ile	missense_variant	4/19	1	NM_020196.3	P1
XAB2	ENST00000595288.5 linkuse as main transcript	n.882G>A		non_coding_transcript_exon_variant	1/11	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

235318

Hom.:

AF XY:

0.0000234

AC XY:

AN XY:

128350

show subpopulations

Gnomad AFR exome

AF:

0.0000676

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000671

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1455120

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723618

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000686

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.075

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0063

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.39

MutationTaster

Benign

0.56

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.24

REVEL

Benign

0.024

Sift

Benign

0.84

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.086

MutPred

0.23

Loss of MoRF binding (P = 0.1296);

MVP

0.093

MPC

0.41

ClinPred

0.017

GERP RS

0.030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.054

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over