17-73257770-C-A

Variant names:

• chr17-73257770-C-A
• rs1265376271
• NM_001129885.1:c.218G>T

Variant summary

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

The NM_001129885.1(CPSF4L):​c.218G>T​(p.Arg73Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,472 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. R73Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CPSF4L NM_001129885.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49
• Publications: 0 publications found

Genes affected

CPSF4L (HGNC:33632): (cleavage and polyadenylation specific factor 4 like) Predicted to enable RNA binding activity and metal ion binding activity. Predicted to be involved in pre-mRNA cleavage required for polyadenylation. Predicted to be part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129885.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF4L	NM_001129885.1	MANE Select	c.218G>T	p.Arg73Leu	missense	Exon 3 of 6	NP_001123357.1	A6NMK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF4L	ENST00000344935.8	TSL:1 MANE Select	c.218G>T	p.Arg73Leu	missense	Exon 3 of 6	ENSP00000343900.4	A6NMK7
	CPSF4L	ENST00000397671.1	TSL:5	c.26G>T	p.Arg9Leu	missense	Exon 3 of 7	ENSP00000380788.1	H9KVA5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399472 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690248

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078978

Other (OTH) AF: 0.00 AC: 0 AN: 58034

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.058	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.5
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.58		Loss of MoRF binding (P = 0.002)
MVP		0.24
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.53
gMVP		0.88
Mutation Taster		=65/35	polymorphism

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: rs1265376271; hg19: chr17-71253909;