2-152659162-G-T

Variant names:

• chr2-152659162-G-T
• rs1685613294
• NM_001365597.4:c.2563C>A

Variant summary

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

The NM_001365597.4(PRPF40A):​c.2563C>A​(p.His855Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRPF40A NM_001365597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92
• 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.2563C>A	p.His855Asn	missense	Exon 23 of 26	NP_001352526.1	F5H578
	PRPF40A	NM_001395488.1		c.2629C>A	p.His877Asn	missense	Exon 23 of 26	NP_001382417.1	A0A7N4I394
	PRPF40A	NM_001365596.4		c.2575C>A	p.His859Asn	missense	Exon 23 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.2563C>A	p.His855Asn	missense	Exon 23 of 26	ENSP00000444656.4	F5H578
	PRPF40A	ENST00000410080.8	TSL:5	c.2629C>A	p.His877Asn	missense	Exon 23 of 26	ENSP00000386458.4	A0A7N4I394
	PRPF40A	ENST00000968845.1		c.2575C>A	p.His859Asn	missense	Exon 23 of 26	ENSP00000638904.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461638 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

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	Benign	0.10
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
PhyloP100		9.9
PrimateAI	Uncertain	0.77	T
REVEL	Benign	0.17
MVP		0.55
MPC		0.68
ClinPred		0.77	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.31
Mutation Taster		=64/36	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: rs1685613294; hg19: chr2-153515676;