2-152670345-C-T

Variant names:

• chr2-152670345-C-T
• NM_001365597.4:c.1642G>A

Variant summary

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

The NM_001365597.4(PRPF40A):​c.1642G>A​(p.Ala548Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRPF40A NM_001365597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

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]

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_001365597.4. 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
	PRPF40A	NM_001365597.4	MANE Select	c.1642G>A	p.Ala548Thr	missense	Exon 15 of 26	NP_001352526.1	F5H578
	PRPF40A	NM_001395488.1		c.1708G>A	p.Ala570Thr	missense	Exon 15 of 26	NP_001382417.1	A0A7N4I394
	PRPF40A	NM_001365596.4		c.1642G>A	p.Ala548Thr	missense	Exon 15 of 26	NP_001352525.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF40A	ENST00000545856.8	TSL:1 MANE Select	c.1642G>A	p.Ala548Thr	missense	Exon 15 of 26	ENSP00000444656.4	F5H578
	PRPF40A	ENST00000410080.8	TSL:5	c.1708G>A	p.Ala570Thr	missense	Exon 15 of 26	ENSP00000386458.4	A0A7N4I394
	PRPF40A	ENST00000968845.1		c.1642G>A	p.Ala548Thr	missense	Exon 15 of 26	ENSP00000638904.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.79	T
PhyloP100		7.9
PrimateAI	Pathogenic	0.83	D
REVEL	Benign	0.22
MVP		0.47
MPC		1.4
ClinPred		0.89	D
GERP RS		5.2
gMVP		0.53
Mutation Taster		=33/67	disease causing

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

hg19: chr2-153526859;