rs1173996006

Variant names:

• chr19-35743834-G-A
• rs1173996006
• NM_001040425.3:c.436C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-35743834-G-A
• chr19-35743834-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040425.3(U2AF1L4):​c.436C>T​(p.Leu146Phe) 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 1,460,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. L146V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: U2AF1L4 NM_001040425.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33396822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
U2AF1L4	NM_001040425.3	c.436C>T	p.Leu146Phe	missense_variant	Exon 5 of 6	ENST00000378975.8	NP_001035515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
U2AF1L4	ENST00000378975.8	c.436C>T	p.Leu146Phe	missense_variant	Exon 5 of 6	1	NM_001040425.3	ENSP00000368258.2
ENSG00000267120	ENST00000589807.1	n.*197C>T		non_coding_transcript_exon_variant	Exon 6 of 11	2		ENSP00000472696.1
ENSG00000267120	ENST00000589807.1	n.*197C>T		3_prime_UTR_variant	Exon 6 of 11	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460712 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726592

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111498

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	0.068
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.59	T
PhyloP100		1.2
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;D
Vest4		0.41
MutPred		0.46		Gain of loop (P = 0.0045);.;
MVP		0.13
ClinPred		0.46	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1173996006; hg19: chr19-36234735; COSMIC: COSV53075701; COSMIC: COSV53075701;