19-35743751-T-A

Variant names:

• chr19-35743751-T-A
• rs17638853
• NM_001040425.3:c.461+58A>T

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.461+58A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,138,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: U2AF1L4 NM_001040425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• 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 (REVEL=0.026).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040425.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1L4	NM_001040425.3	MANE Select	c.461+58A>T		intron	N/A	NP_001035515.1
	U2AF1L4	NM_144987.4		c.403+58A>T		intron	N/A	NP_659424.2
	U2AF1L4	NM_001369824.2		c.403+58A>T		intron	N/A	NP_001356753.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1L4	ENST00000378975.8	TSL:1 MANE Select	c.461+58A>T		intron	N/A	ENSP00000368258.2
	U2AF1L4	ENST00000292879.9	TSL:1	c.403+58A>T		intron	N/A	ENSP00000292879.4
	U2AF1L4	ENST00000587987.5	TSL:1	n.*429+58A>T		intron	N/A	ENSP00000465170.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000351 AC: 4 AN: 1138020 Hom.: 0 Cov.: 19 AF XY: 0.00000348 AC XY: 2 AN XY: 574236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000373 AC: 1 AN: 26794

American (AMR) AF: 0.00 AC: 0 AN: 37128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23374

East Asian (EAS) AF: 0.00 AC: 0 AN: 35188

South Asian (SAS) AF: 0.00 AC: 0 AN: 76194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5056

European-Non Finnish (NFE) AF: 0.00000359 AC: 3 AN: 836428

Other (OTH) AF: 0.00 AC: 0 AN: 49468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.4
DANN	Benign	0.82
PhyloP100		-0.14

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

Other links and lift over

dbSNP: rs17638853; hg19: chr19-36234652;