chr19-35744142-G-C

Variant names:

• chr19-35744142-G-C
• rs766548750
• NM_001040425.3:c.235C>G

Variant summary

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

The NM_001040425.3(U2AF1L4):​c.235C>G​(p.Arg79Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R79W) 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: 4.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
U2AF1L4	NM_001040425.3	c.235C>G	p.Arg79Gly	missense_variant	Exon 4 of 6	ENST00000378975.8	NP_001035515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
U2AF1L4	ENST00000378975.8	c.235C>G	p.Arg79Gly	missense_variant	Exon 4 of 6	1	NM_001040425.3	ENSP00000368258.2
ENSG00000267120	ENST00000589807.1	n.*54C>G		non_coding_transcript_exon_variant	Exon 5 of 11	2		ENSP00000472696.1
ENSG00000267120	ENST00000589807.1	n.*54C>G		3_prime_UTR_variant	Exon 5 of 11	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461222 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726850

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111752

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.
PhyloP100		4.7
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.021	D;D;D
Sift4G	Benign	0.10	T;T;D
Polyphen		0.87	P;P;P
Vest4		0.80
MutPred		0.36		Loss of stability (P = 0.108);.;.;
MVP		0.23
MPC		0.18
ClinPred		0.86	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.52
Mutation Taster		=78/22	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: rs766548750; hg19: chr19-36235043;