1-154225211-C-A

Variant names:

• chr1-154225211-C-A
• NM_014847.4:c.88C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014847.4(UBAP2L):​c.88C>A​(p.Gln30Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAP2L NM_014847.4 missense, splice_region
• Scores: Splicing: ADA: 0.9697
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP2L	NM_014847.4	c.88C>A	p.Gln30Lys	missense_variant, splice_region_variant	Exon 2 of 27	ENST00000428931.6	NP_055662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP2L	ENST00000428931.6	c.88C>A	p.Gln30Lys	missense_variant, splice_region_variant	Exon 2 of 27	5	NM_014847.4	ENSP00000389445.1

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

Apr 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88C>A (p.Q30K) alteration is located in exon 2 (coding exon 1) of the UBAP2L gene. This alteration results from a C to A substitution at nucleotide position 88, causing the glutamine (Q) at amino acid position 30 to be replaced by a lysine (K). 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	0.76
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	.;.;D;T;T;T;T;T;T;D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;T;T;T;D;D;T;D;D;.
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.42	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M;.;.;.;.;.;.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.9	D;.;D;D;D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.092	T;.;T;D;T;T;T;T;T;T
Sift4G	Uncertain	0.024	D;D;D;D;T;T;T;T;T;D
Polyphen		0.95	P;P;P;D;.;.;.;.;.;P
Vest4		0.64
MutPred		0.17		Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);
MVP		0.52
MPC		0.86
ClinPred		0.97	D
GERP RS		5.3
PromoterAI		0.0059	Neutral
Varity_R		0.60
gMVP		0.66
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Pathogenic	0.84
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: chr1-154197687;