NM_020196.3:c.51+342T>G

Variant names:

• chr19-7629135-A-C
• rs4134813
• NM_020196.3:c.51+342T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020196.3(XAB2):​c.51+342T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,032 control chromosomes in the GnomAD database, including 8,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8591 hom., cov: 32)
• Consequence: XAB2 NM_020196.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XAB2	NM_020196.3	c.51+342T>G		intron_variant	Intron 1 of 18	ENST00000358368.5	NP_064581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XAB2	ENST00000358368.5	c.51+342T>G		intron_variant	Intron 1 of 18	1	NM_020196.3	ENSP00000351137.3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50328 AN: 151914 Hom.: 8584 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50357 AN: 152032 Hom.: 8591 Cov.: 32 AF XY: 0.334 AC XY: 24833 AN XY: 74296

African (AFR) AF: 0.251 AC: 10414 AN: 41472

American (AMR) AF: 0.368 AC: 5619 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5180

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4812

European-Finnish (FIN) AF: 0.452 AC: 4755 AN: 10530

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24970 AN: 67982

Other (OTH) AF: 0.342 AC: 720 AN: 2108

Alfa AF: 0.356 Hom.: 11864

Bravo AF: 0.320

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.49
PhyloP100		-1.4
PromoterAI		0.0041	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs4134813; hg19: chr19-7694021;