19-7619765-T-A

Variant names:

• chr19-7619765-T-A
• rs1327493247
• NM_020196.3:c.2488A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020196.3(XAB2):​c.2488A>T​(p.Met830Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M830V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: XAB2 NM_020196.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07075432).

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.2488A>T	p.Met830Leu	missense	Exon 18 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.2488A>T	p.Met830Leu	missense	Exon 18 of 19	ENSP00000351137.3	Q9HCS7
	XAB2	ENST00000925818.1		c.2518A>T	p.Met840Leu	missense	Exon 18 of 19	ENSP00000595877.1
	XAB2	ENST00000925815.1		c.2485A>T	p.Met829Leu	missense	Exon 18 of 19	ENSP00000595874.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.052
Sift	Benign	0.19	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.37
MutPred		0.18		Loss of stability (P = 0.1914)
MVP		0.068
MPC		0.47
ClinPred		0.17	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.15
Mutation Taster		=97/3	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

dbSNP: rs1327493247; hg19: chr19-7684651;