19-35742670-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144987.4(U2AF1L4):​c.537G>C​(p.Trp179Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

U2AF1L4
NM_144987.4 missense

Scores

1
1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.465
Variant links:
Genes affected
U2AF1L4 (HGNC:23020): (U2 small nuclear RNA auxiliary factor 1 like 4) Predicted to enable pre-mRNA 3'-splice site binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be part of U2AF complex and spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]
IGFLR1 (HGNC:23620): (IGF like family receptor 1) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.074695736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
U2AF1L4NM_001040425.3 linkc.*49G>C 3_prime_UTR_variant Exon 6 of 6 ENST00000378975.8 NP_001035515.1 Q8WU68-3
IGFLR1NM_024660.4 linkc.-318G>C upstream_gene_variant ENST00000246532.6 NP_078936.1 Q9H665-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
U2AF1L4ENST00000378975 linkc.*49G>C 3_prime_UTR_variant Exon 6 of 6 1 NM_001040425.3 ENSP00000368258.2 Q8WU68-3
ENSG00000267120ENST00000589807.1 linkn.*223-51G>C intron_variant Intron 6 of 10 2 ENSP00000472696.1 M0R2N4
IGFLR1ENST00000246532.6 linkc.-318G>C upstream_gene_variant 1 NM_024660.4 ENSP00000246532.1 Q9H665-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250030
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135172
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460776
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726640
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.537G>C (p.W179C) alteration is located in exon 6 (coding exon 6) of the U2AF1L4 gene. This alteration results from a G to C substitution at nucleotide position 537, causing the tryptophan (W) at amino acid position 179 to be replaced by a cysteine (C). 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
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
5.8
DANN
Benign
0.96
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.075
T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.035
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.059
T
Polyphen
0.0020
B
Vest4
0.23
MutPred
0.38
Gain of disorder (P = 0.0645);
MVP
0.055
MPC
0.65
ClinPred
0.68
D
GERP RS
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1334740707; hg19: chr19-36233571; API