dbSNP rs794078: XAB2:p.Thr620Thr (chr19-7620957-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020196.3(XAB2):c.1860C>T(p.Thr620Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,582,630 control chromosomes in the GnomAD database, including 33,659 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 0.18 ( 2550 hom., cov: 33)

Exomes 𝑓: 0.21 ( 31109 hom. )

Consequence

XAB2
NM_020196.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Publications

29 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=-0.021 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XAB2	NM_020196.3 link	c.1860C>T	p.Thr620Thr	synonymous_variant	Exon 14 of 19	ENST00000358368.5	NP_064581.2	Q9HCS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XAB2	ENST00000358368.5 link	c.1860C>T	p.Thr620Thr	synonymous_variant	Exon 14 of 19	1	NM_020196.3	ENSP00000351137.3	Q9HCS7
XAB2	ENST00000595288.5 link	n.3588C>T		non_coding_transcript_exon_variant	Exon 8 of 11	2
XAB2	ENST00000596134.1 link	n.479C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
XAB2	ENST00000600230.1 link	n.243C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27033

AN:

152120

Hom.:

2551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.177

AC:

34916

AN:

197120

AF XY:

0.177

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.205

AC:

293510

AN:

1430392

Hom.:

31109

Cov.:

AF XY:

0.203

AC XY:

143841

AN XY:

708416

show subpopulations

African (AFR)

AF:

0.137

AC:

4551

AN:

33260

American (AMR)

AF:

0.145

AC:

5572

AN:

38472

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4272

AN:

25478

East Asian (EAS)

AF:

0.135

AC:

5219

AN:

38616

South Asian (SAS)

AF:

0.132

AC:

10831

AN:

81888

European-Finnish (FIN)

AF:

0.197

AC:

9813

AN:

49766

Middle Eastern (MID)

AF:

0.181

AC:

1031

AN:

5710

European-Non Finnish (NFE)

AF:

0.219

AC:

240522

AN:

1097814

Other (OTH)

AF:

0.197

AC:

11699

AN:

59388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

14955

29911

44866

59822

74777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8322

16644

24966

33288

41610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.178

AC:

27045

AN:

152238

Hom.:

2550

Cov.:

AF XY:

0.175

AC XY:

13020

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.138

AC:

5739

AN:

41558

American (AMR)

AF:

0.160

AC:

2455

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

560

AN:

3472

East Asian (EAS)

AF:

0.116

AC:

600

AN:

5170

South Asian (SAS)

AF:

0.132

AC:

639

AN:

4824

European-Finnish (FIN)

AF:

0.185

AC:

1961

AN:

10606

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14234

AN:

67986

Other (OTH)

AF:

0.175

AC:

370

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1155

2310

3464

4619

5774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

9304

Bravo

AF:

0.178

Asia WGS

AF:

0.129

AC:

449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.0

(source)

DANN

Benign

0.86

PhyloP100

-0.021

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over