chr7-114068445-G-A

Variant names:

• chr7-114068445-G-A
• rs2035980
• ENST00000449795.5:c.-182+7181C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000449795.5(PPP1R3A):​c.-182+7181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,952 control chromosomes in the GnomAD database, including 28,526 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28526 hom., cov: 32)
• Consequence: PPP1R3A ENST00000449795.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 1 publications found

Genes affected

PPP1R3A (HGNC:9291): (protein phosphatase 1 regulatory subunit 3A) The glycogen-associated form of protein phosphatase-1 (PP1) derived from skeletal muscle is a heterodimer composed of a 37-kD catalytic subunit and a 124-kD targeting and regulatory subunit. This gene encodes the regulatory subunit which binds to muscle glycogen with high affinity, thereby enhancing dephosphorylation of glycogen-bound substrates for PP1 such as glycogen synthase and glycogen phosphorylase kinase. [provided by RefSeq, Jul 2008]

PPP1R3A Gene-Disease associations (from GenCC):

• diabetes mellitus, noninsulin-dependent

  Inheritance: Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000449795.5	c.-182+7181C>T		intron_variant	Intron 1 of 3	3		ENSP00000401278.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92632 AN: 151832 Hom.: 28512 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.610 AC: 92698 AN: 151952 Hom.: 28526 Cov.: 32 AF XY: 0.618 AC XY: 45908 AN XY: 74284

African (AFR) AF: 0.520 AC: 21531 AN: 41430

American (AMR) AF: 0.571 AC: 8702 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3468

East Asian (EAS) AF: 0.669 AC: 3458 AN: 5172

South Asian (SAS) AF: 0.717 AC: 3454 AN: 4814

European-Finnish (FIN) AF: 0.751 AC: 7930 AN: 10558

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.637 AC: 43259 AN: 67952

Other (OTH) AF: 0.626 AC: 1317 AN: 2104

Alfa AF: 0.625 Hom.: 7703

Bravo AF: 0.591

Asia WGS AF: 0.627 AC: 2181 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.74
PhyloP100		-0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2035980; hg19: chr7-113708500;