chr19-35742798-G-C

Variant names:

• chr19-35742798-G-C
• rs906863029
• NM_001040425.3:c.467C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040425.3(U2AF1L4):​c.467C>G​(p.Pro156Arg) 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. 14/19 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. P156L) 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: 2.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14255753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
U2AF1L4	NM_001040425.3	c.467C>G	p.Pro156Arg	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.467C>G	p.Pro156Arg	missense_variant	Exon 6 of 6	1	NM_001040425.3	ENSP00000368258.2
ENSG00000267120	ENST00000589807.1	n.*223-179C>G		intron_variant	Intron 6 of 10	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	0.029
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.72	N
REVEL	Benign	0.24
Sift	Uncertain	0.025	D
Sift4G	Benign	0.65	T
Polyphen		0.45	B
Vest4		0.36
MutPred		0.27		Loss of glycosylation at P137 (P = 0.0988);
MVP		0.22
MPC		0.12
ClinPred		0.67	D
GERP RS		3.9
PromoterAI		-0.0093	Neutral
Varity_R		0.017
gMVP		0.070
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs906863029; hg19: chr19-36233699;