2-152657909-T-C

Variant names:

• chr2-152657909-T-C
• rs759084868
• NM_001365597.4:c.2806A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001365597.4(PRPF40A):​c.2806A>G​(p.Lys936Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,452,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PRPF40A NM_001365597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18382451).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

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.2806A>G	p.Lys936Glu	missense	Exon 25 of 26	NP_001352526.1	F5H578
	PRPF40A	NM_001395488.1		c.2872A>G	p.Lys958Glu	missense	Exon 25 of 26	NP_001382417.1	A0A7N4I394
	PRPF40A	NM_001365596.4		c.2818A>G	p.Lys940Glu	missense	Exon 25 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.2806A>G	p.Lys936Glu	missense	Exon 25 of 26	ENSP00000444656.4	F5H578
	PRPF40A	ENST00000410080.8	TSL:5	c.2872A>G	p.Lys958Glu	missense	Exon 25 of 26	ENSP00000386458.4	A0A7N4I394
	PRPF40A	ENST00000968845.1		c.2818A>G	p.Lys940Glu	missense	Exon 25 of 26	ENSP00000638904.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000426 AC: 1 AN: 235010 AF XY: 0.00000786

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000947

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1452216 Hom.: 0 Cov.: 30 AF XY: 0.00000970 AC XY: 7 AN XY: 721634

African (AFR) AF: 0.0000302 AC: 1 AN: 33164

American (AMR) AF: 0.00 AC: 0 AN: 43270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.0000163 AC: 18 AN: 1107142

Other (OTH) AF: 0.00 AC: 0 AN: 59970

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000371 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Benign	0.69
Eigen	Benign	-0.096
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		5.6
PrimateAI	Pathogenic	0.86	D
REVEL	Benign	0.17
MVP		0.42
MPC		0.86
ClinPred		0.64	D
GERP RS		5.3
gMVP		0.14
Mutation Taster		=85/15	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: rs759084868; hg19: chr2-153514423;