rs869312187

Variant names:

• chr19-54128351-C-A
• rs869312187
• NM_015629.4:c.1120C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54128351-C-A
• chr19-54128351-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015629.4(PRPF31):​c.1120C>A​(p.Gln374Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000716 in 1,396,210 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Q374Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PRPF31 NM_015629.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.50
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• PRPF31-related retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 11

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.280585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	NM_015629.4	MANE Select	c.1120C>A	p.Gln374Lys	missense	Exon 11 of 14	NP_056444.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.1120C>A	p.Gln374Lys	missense	Exon 11 of 14	ENSP00000324122.4
	PRPF31	ENST00000391755.1	TSL:5	c.1102C>A	p.Gln368Lys	missense	Exon 10 of 13	ENSP00000375635.1
	PRPF31	ENST00000419967.5	TSL:5	c.1120C>A	p.Gln374Lys	missense	Exon 11 of 13	ENSP00000405166.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396210 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 688670

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.00 AC: 0 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 35806

South Asian (SAS) AF: 0.00 AC: 0 AN: 79170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078726

Other (OTH) AF: 0.0000173 AC: 1 AN: 57810

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.051
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.042	D
MutationAssessor	Benign	1.5	L
PhyloP100		4.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.35
Sift	Benign	0.94	T
Sift4G	Benign	0.99	T
Polyphen		0.078	B
Vest4		0.35
MutPred		0.55		Gain of ubiquitination at Q374 (P = 0.0094)
MVP		0.67
MPC		1.1
ClinPred		0.71	D
GERP RS		4.5
Varity_R		0.46
gMVP		0.93
Mutation Taster		=75/25	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: rs869312187; hg19: chr19-54631726;