rs387907100

Variant names:

• chr20-64027138-C-A
• rs387907100
• NM_012469.4:c.2185C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-64027138-C-A
• chr20-64027138-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_012469.4(PRPF6):​c.2185C>A​(p.Arg729Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,402 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R729R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PRPF6 NM_012469.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.00
• Publications: 16 publications found

Genes affected

PRPF6 (HGNC:15860): (pre-mRNA processing factor 6) The protein encoded by this gene appears to be involved in pre-mRNA splicing, possibly acting as a bridging factor between U5 and U4/U6 snRNPs in formation of the spliceosome. The encoded protein also can bind androgen receptor, providing a link between transcriptional activation and splicing. [provided by RefSeq, Jul 2008]

PRPF6 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 60

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 20-64027138-C-A is Benign according to our data. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-64027138-C-A is described in CliVar as Likely_benign. Clinvar id is 3028562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF6	NM_012469.4	c.2185C>A	p.Arg729Arg	synonymous_variant	Exon 16 of 21	ENST00000266079.5	NP_036601.2
PRPF6	XM_006723769.4	c.1966C>A	p.Arg656Arg	synonymous_variant	Exon 15 of 20		XP_006723832.1
PRPF6	XR_007067448.1	n.2299C>A		non_coding_transcript_exon_variant	Exon 16 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF6	ENST00000266079.5	c.2185C>A	p.Arg729Arg	synonymous_variant	Exon 16 of 21	1	NM_012469.4	ENSP00000266079.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461402 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal dystrophy Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.6
DANN	Benign	0.54
PhyloP100		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs387907100; hg19: chr20-62658491;