19-7619626-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020196.3(XAB2):​c.2528G>A​(p.Ser843Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,451,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

XAB2
NM_020196.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11678362).
BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XAB2NM_020196.3 linkc.2528G>A p.Ser843Asn missense_variant Exon 19 of 19 ENST00000358368.5 NP_064581.2 Q9HCS7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XAB2ENST00000358368.5 linkc.2528G>A p.Ser843Asn missense_variant Exon 19 of 19 1 NM_020196.3 ENSP00000351137.3 Q9HCS7
XAB2ENST00000595288.5 linkn.4455G>A non_coding_transcript_exon_variant Exon 11 of 11 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1451280
Hom.:
0
Cov.:
36
AF XY:
0.00000694
AC XY:
5
AN XY:
720952
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000136
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2528G>A (p.S843N) alteration is located in exon 19 (coding exon 19) of the XAB2 gene. This alteration results from a G to A substitution at nucleotide position 2528, causing the serine (S) at amino acid position 843 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T
Eigen
Benign
0.055
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.39
N
LIST_S2
Uncertain
0.88
D
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.067
Sift
Benign
0.070
T
Sift4G
Benign
0.19
T
Polyphen
0.20
B
Vest4
0.46
MutPred
0.23
Gain of relative solvent accessibility (P = 0.0082);
MVP
0.23
MPC
0.58
ClinPred
0.36
T
GERP RS
4.9
Varity_R
0.089
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7684512; API