chr5-6449223-C-G

Variant names:

• chr5-6449223-C-G
• NM_001145161.3:c.330C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145161.3(UBE2QL1):​c.330C>G​(p.Phe110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: UBE2QL1 NM_001145161.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0310

Genes affected

UBE2QL1 (HGNC:37269): (ubiquitin conjugating enzyme E2 Q family like 1) Enables ubiquitin conjugating enzyme activity. Predicted to be involved in protein polyubiquitination. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374639 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19713363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2QL1	NM_001145161.3	c.330C>G	p.Phe110Leu	missense_variant	Exon 1 of 2	ENST00000399816.4	NP_001138633.1
LOC105374639	XR_007058679.1	n.-114C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2QL1	ENST00000399816.4	c.330C>G	p.Phe110Leu	missense_variant	Exon 1 of 2	1	NM_001145161.3	ENSP00000382713.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.66e-7 AC: 1 AN: 1305814 Hom.: 0 Cov.: 34 AF XY: 0.00000157 AC XY: 1 AN XY: 636192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000452

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.330C>G (p.F110L) alteration is located in exon 1 (coding exon 1) of the UBE2QL1 gene. This alteration results from a C to G substitution at nucleotide position 330, causing the phenylalanine (F) at amino acid position 110 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Benign	0.19	T
Sift4G	Benign	0.16	T
Polyphen		0.064	B
Vest4		0.56
MutPred		0.52		Gain of MoRF binding (P = 0.1103);
MVP		0.048
ClinPred		0.70	D
GERP RS		2.4
Varity_R		0.36
gMVP		0.81

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: chr5-6449336;