1-154243248-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_014847.4(UBAP2L):c.788A>T(p.Asn263Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAP2L NM_014847.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

Genes affected

UBAP2L (HGNC:29877): (ubiquitin associated protein 2 like) Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, UBAP2L
• BP4: Computational evidence support a benign effect (MetaRNN=0.2145817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBAP2L	NM_014847.4	c.788A>T	p.Asn263Ile	missense_variant	10/27	ENST00000428931.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBAP2L	ENST00000428931.6	c.788A>T	p.Asn263Ile	missense_variant	10/27	5	NM_014847.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Feb 28, 2024

The c.788A>T (p.N263I) alteration is located in exon 10 (coding exon 9) of the UBAP2L gene. This alteration results from a A to T substitution at nucleotide position 788, causing the asparagine (N) at amino acid position 263 to be replaced by an isoleucine (I). 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	Benign	0.30
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Benign	-0.0070
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;L;.;.;.;.;L
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	N;.;N;N;N;D;D;N
REVEL	Benign	0.097
Sift	Uncertain	0.0060	D;.;D;D;T;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D;T;D;D
Polyphen		0.36	B;B;B;D;.;.;.;B
Vest4		0.61
MutPred		0.40		Loss of catalytic residue at N263 (P = 0.0177);.;Loss of catalytic residue at N263 (P = 0.0177);.;Loss of catalytic residue at N263 (P = 0.0177);.;.;Loss of catalytic residue at N263 (P = 0.0177);
MVP		0.22
MPC		0.85
ClinPred		0.84	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-154215724;