chr1-154246295-C-A

Position:

• chr1-154246295-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_014847.4(UBAP2L):​c.934C>A​(p.Gln312Lys) 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: 32)
• Consequence: UBAP2L NM_014847.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, UBAP2L

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBAP2L	NM_014847.4	c.934C>A	p.Gln312Lys	missense_variant	11/27	ENST00000428931.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBAP2L	ENST00000428931.6	c.934C>A	p.Gln312Lys	missense_variant	11/27	5	NM_014847.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 14, 2023

The c.934C>A (p.Q312K) alteration is located in exon 11 (coding exon 10) of the UBAP2L gene. This alteration results from a C to A substitution at nucleotide position 934, causing the glutamine (Q) at amino acid position 312 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	Benign	0.20
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;.
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	2.9	M;.;M;.;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.4	N;.;N;N;D;N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;.;D;D;D;D
Sift4G	Uncertain	0.028	D;D;T;T;D;T
Polyphen		0.51	P;P;B;D;.;B
Vest4		0.77
MutPred		0.31		Gain of ubiquitination at Q312 (P = 0.0042);.;Gain of ubiquitination at Q312 (P = 0.0042);.;.;Gain of ubiquitination at Q312 (P = 0.0042);
MVP		0.59
MPC		0.86
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.56
gMVP		0.69

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: chr1-154218771;