rs1288700877

Variant names:

• chr19-35742753-C-A
• rs1288700877
• NM_001040425.3:c.512G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-35742753-C-A
• chr19-35742753-C-T

Variant summary

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

The NM_001040425.3(U2AF1L4):​c.512G>T​(p.Arg171Leu) 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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R171Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: U2AF1L4 NM_001040425.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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]

ENSG00000267120 (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=0.17189863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
U2AF1L4	NM_001040425.3	c.512G>T	p.Arg171Leu	missense_variant	Exon 6 of 6	ENST00000378975.8	NP_001035515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
U2AF1L4	ENST00000378975.8	c.512G>T	p.Arg171Leu	missense_variant	Exon 6 of 6	1	NM_001040425.3	ENSP00000368258.2
ENSG00000267120	ENST00000589807.1	n.*223-134G>T		intron_variant	Intron 6 of 10	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Uncertain	0.98
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.40		Loss of glycosylation at T150 (P = 0.033);
MVP		0.092
MPC		0.27
ClinPred		0.88	D
GERP RS		4.4
gMVP		0.17

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

Other links and lift over

dbSNP: rs1288700877; hg19: chr19-36233654;