2-152694586-T-A

Position:

• chr2-152694586-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395483.1(PRPF40A):​c.-468A>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: PRPF40A NM_001395483.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88

Genes affected

PRPF40A (HGNC:16463): (pre-mRNA processing factor 40 homolog A) Enables RNA binding activity. Involved in several processes, including cytoskeleton organization; regulation of cell shape; and regulation of cytokinesis. Located in nuclear matrix and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

PRPF40A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18696895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF40A	NM_001365597.4	c.379A>T	p.Met127Leu	missense_variant	3/26	ENST00000545856.8	NP_001352526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF40A	ENST00000545856.8	c.379A>T	p.Met127Leu	missense_variant	3/26	1	NM_001365597.4	ENSP00000444656.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.253A>T (p.M85L) alteration is located in exon 3 (coding exon 3) of the PRPF40A gene. This alteration results from a A to T substitution at nucleotide position 253, causing the methionine (M) at amino acid position 85 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Benign	0.92
Eigen	Benign	0.011
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	T;T;T;T;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.46	.;.;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.47	.;.;T;T;T
Sift4G	Benign	0.60	.;.;.;T;.
MutPred		0.37		.;.;Loss of helix (P = 0.0033);.;.;
MVP		0.55
MPC		0.61
ClinPred		0.53	D
GERP RS		5.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
gMVP		0.21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-153551100;