19-54123802-C-T

Variant names:

• chr19-54123802-C-T
• rs119475043
• NM_015629.4:c.581C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1 PP3 BS2

The NM_015629.4(PRPF31):​c.581C>T​(p.Ala194Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,460,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PRPF31 NM_015629.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

Genes affected

PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

PRPF31-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM1: In a helix (size 34) in uniprot entity PRP31_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_015629.4
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.581C>T	p.Ala194Val	missense_variant	Exon 7 of 14	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.581C>T	p.Ala194Val	missense_variant	Exon 7 of 14		XP_006723200.1
PRPF31	XM_047438587.1	c.581C>T	p.Ala194Val	missense_variant	Exon 7 of 10		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.581C>T	p.Ala194Val	missense_variant	Exon 7 of 14	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460530 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 726688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	.;T;T;.;T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;.;D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.054	T;D;D;D;D;D
Sift4G	Benign	0.090	T;D;T;T;T;D
Polyphen		0.96	.;D;.;.;.;.
Vest4		0.83
MutPred		0.68		Loss of disorder (P = 0.0737);Loss of disorder (P = 0.0737);Loss of disorder (P = 0.0737);Loss of disorder (P = 0.0737);Loss of disorder (P = 0.0737);Loss of disorder (P = 0.0737);
MVP		0.66
MPC		1.1
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.68
gMVP		0.90

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

LitVar

Other links and lift over

dbSNP: rs119475043; hg19: chr19-54627181; COSMIC: COSV100319878; COSMIC: COSV100319878;