19-7619608-A-G

Position:

• chr19-7619608-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020196.3(XAB2):​c.2546T>C​(p.Phe849Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: XAB2 NM_020196.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XAB2	NM_020196.3	c.2546T>C	p.Phe849Ser	missense_variant	19/19	ENST00000358368.5	NP_064581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XAB2	ENST00000358368.5	c.2546T>C	p.Phe849Ser	missense_variant	19/19	1	NM_020196.3	ENSP00000351137.3
XAB2	ENST00000595288.5	n.4473T>C		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.2546T>C (p.F849S) alteration is located in exon 19 (coding exon 19) of the XAB2 gene. This alteration results from a T to C substitution at nucleotide position 2546, causing the phenylalanine (F) at amino acid position 849 to be replaced by a serine (S). 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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.43		Gain of loop (P = 0.0195);
MVP		0.17
MPC		1.9
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.90
gMVP		0.79

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: chr19-7684494;