Variant 19-55230541-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014931.4(PPP6R1):c.2643-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,613,578 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 93 hom. )

Consequence

PPP6R1
NM_014931.4 intron

Scores

Splicing: ADA: 0.00008761

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0290

Variant links:

Genes affected

PPP6R1 (HGNC:29195): (protein phosphatase 6 regulatory subunit 1) Protein phosphatase regulatory subunits, such as SAPS1, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS1 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).[supplied by OMIM, Nov 2010]

PPP6R1 links:

PPP6R1 (HGNC:):

PPP6R1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-55230541-G-A is Benign according to our data. Variant chr19-55230541-G-A is described in ClinVar as [Benign]. Clinvar id is 769050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R1	NM_014931.4 linkuse as main transcript	c.2643-10C>T		intron_variant		ENST00000412770.7	NP_055746.3	Q9UPN7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PPP6R1	ENST00000412770.7 linkuse as main transcript	c.2643-10C>T	intron_variant	1	NM_014931.4	ENSP00000414202.1	Q9UPN7
PPP6R1	ENST00000587283.5 linkuse as main transcript	c.2643-10C>T	intron_variant	1		ENSP00000467521.1	Q9UPN7
PPP6R1	ENST00000587457.1 linkuse as main transcript	n.1638-10C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2767

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00450

AC:

1114

AN:

247682

Hom.:

AF XY:

0.00339

AC XY:

457

AN XY:

134798

show subpopulations

Gnomad AFR exome

AF:

0.0646

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000537

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00186

AC:

2725

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1157

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0689

Gnomad4 AMR exome

AF:

0.00327

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.0182

AC:

2772

AN:

152282

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1250

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0638

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over