chr19-7619626-C-T

Variant names:

• chr19-7619626-C-T
• NM_020196.3:c.2528G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020196.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XAB2	NM_020196.3	MANE Select	c.2528G>A	p.Ser843Asn	missense	Exon 19 of 19	NP_064581.2	Q9HCS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XAB2	ENST00000358368.5	TSL:1 MANE Select	c.2528G>A	p.Ser843Asn	missense	Exon 19 of 19	ENSP00000351137.3	Q9HCS7
	XAB2	ENST00000925818.1		c.2558G>A	p.Ser853Asn	missense	Exon 19 of 19	ENSP00000595877.1
	XAB2	ENST00000925815.1		c.2525G>A	p.Ser842Asn	missense	Exon 19 of 19	ENSP00000595874.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25266

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 84688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1106670

Other (OTH) AF: 0.00 AC: 0 AN: 59898

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.1
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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr19-7684512;