20-63981306-C-T

Variant names:

• chr20-63981306-C-T
• rs775751428
• NM_012469.4:c.61C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_012469.4(PRPF6):​c.61C>T​(p.Leu21Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000817 in 1,602,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000079 (1 hom.)
• Consequence: PRPF6 NM_012469.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 3.77

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 20-63981306-C-T is Benign according to our data. Variant chr20-63981306-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 898313.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• BS2: High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF6	NM_012469.4	c.61C>T	p.Leu21Leu	synonymous_variant	Exon 1 of 21	ENST00000266079.5	NP_036601.2
PRPF6	XM_006723769.4	c.61C>T	p.Leu21Leu	synonymous_variant	Exon 1 of 20		XP_006723832.1
PRPF6	XR_007067448.1	n.175C>T		non_coding_transcript_exon_variant	Exon 1 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF6	ENST00000266079.5	c.61C>T	p.Leu21Leu	synonymous_variant	Exon 1 of 21	1	NM_012469.4	ENSP00000266079.4

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000139 AC: 31 AN: 222780 Hom.: 0 AF XY: 0.000131 AC XY: 16 AN XY: 121732

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00106

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000280

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000815

Gnomad OTH exome AF: 0.000183

GnomAD4 exome AF: 0.0000793 AC: 115 AN: 1450430 Hom.: 1 Cov.: 31 AF XY: 0.0000860 AC XY: 62 AN XY: 720604

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000923

Gnomad4 ASJ exome AF: 0.00135

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.000307

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000307

Gnomad4 OTH exome AF: 0.000201

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74344

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.000248 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Retinitis pigmentosa Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided Benign:1

Aug 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs775751428; hg19: chr20-62612659;