7-94910224-C-T

Variant names:

• chr7-94910224-C-T
• rs12536183
• NM_001166160.2:c.111C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001166160.2(PPP1R9A):​c.111C>T​(p.Pro37Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 1,613,752 control chromosomes in the GnomAD database, including 7,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.082 (639 hom., cov: 32)
  • Exomes 𝑓: 0.095 (7312 hom.)
• Consequence: PPP1R9A NM_001166160.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.140
• Publications: 12 publications found

Genes affected

PPP1R9A (HGNC:14946): (protein phosphatase 1 regulatory subunit 9A) This gene is imprinted, and located in a cluster of imprinted genes on chromosome 7q12. This gene is transcribed in both neuronal and multiple embryonic tissues, and it is maternally expressed mainly in embryonic skeletal muscle tissues and biallelically expressed in other embryonic tissues. The protein encoded by this gene includes a PDZ domain and a sterile alpha motif (SAM). It is a regulatory subunit of protein phosphatase I, and controls actin cytoskeleton reorganization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 7-94910224-C-T is Benign according to our data. Variant chr7-94910224-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060118.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	NM_001166160.2	MANE Select	c.111C>T	p.Pro37Pro	synonymous	Exon 2 of 20	NP_001159632.1	Q9ULJ8-3
	PPP1R9A	NM_001166161.1		c.111C>T	p.Pro37Pro	synonymous	Exon 1 of 18	NP_001159633.1	Q9ULJ8-5
	PPP1R9A	NM_001166162.1		c.111C>T	p.Pro37Pro	synonymous	Exon 1 of 17	NP_001159634.1	Q9ULJ8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	ENST00000433360.6	TSL:1 MANE Select	c.111C>T	p.Pro37Pro	synonymous	Exon 2 of 20	ENSP00000405514.1	Q9ULJ8-3
	PPP1R9A	ENST00000289495.7	TSL:1	c.111C>T	p.Pro37Pro	synonymous	Exon 1 of 18	ENSP00000289495.7	Q9ULJ8-5
	PPP1R9A	ENST00000456331.6	TSL:1	c.111C>T	p.Pro37Pro	synonymous	Exon 1 of 17	ENSP00000402893.2	Q9ULJ8-4

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12534 AN: 151950 Hom.: 635 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.112 AC: 28046 AN: 251152 AF XY: 0.109

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0872

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0947 AC: 138369 AN: 1461684 Hom.: 7312 Cov.: 32 AF XY: 0.0950 AC XY: 69074 AN XY: 727130

African (AFR) AF: 0.0306 AC: 1023 AN: 33478

American (AMR) AF: 0.219 AC: 9766 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2877 AN: 26136

East Asian (EAS) AF: 0.150 AC: 5967 AN: 39698

South Asian (SAS) AF: 0.121 AC: 10398 AN: 86232

European-Finnish (FIN) AF: 0.103 AC: 5499 AN: 53390

Middle Eastern (MID) AF: 0.115 AC: 663 AN: 5768

European-Non Finnish (NFE) AF: 0.0864 AC: 96037 AN: 1111908

Other (OTH) AF: 0.102 AC: 6139 AN: 60390

GnomAD4 genome AF: 0.0825 AC: 12544 AN: 152068 Hom.: 639 Cov.: 32 AF XY: 0.0851 AC XY: 6324 AN XY: 74332

African (AFR) AF: 0.0311 AC: 1289 AN: 41510

American (AMR) AF: 0.155 AC: 2368 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3466

East Asian (EAS) AF: 0.141 AC: 726 AN: 5142

South Asian (SAS) AF: 0.124 AC: 596 AN: 4804

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0845 AC: 5744 AN: 67978

Other (OTH) AF: 0.101 AC: 213 AN: 2108

Alfa AF: 0.0848 Hom.: 1607

Bravo AF: 0.0847

Asia WGS AF: 0.122 AC: 425 AN: 3478

EpiCase AF: 0.0896

EpiControl AF: 0.0875

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPP1R9A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		-0.14
PromoterAI		-0.0076	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs12536183; hg19: chr7-94539536; COSMIC: COSV56894241;