7-95268489-T-C

Variant names:

• chr7-95268489-T-C
• rs854522
• NM_001166160.2:c.2666-61T>C

Variant summary

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

The NM_001166160.2(PPP1R9A):​c.2666-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,573,008 control chromosomes in the GnomAD database, including 138,331 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 0.37 (10979 hom., cov: 31)
  • Exomes 𝑓: 0.42 (127352 hom.)
• Consequence: PPP1R9A NM_001166160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	NM_001166160.2	MANE Select	c.2666-61T>C		intron	N/A	NP_001159632.1
	PPP1R9A	NM_001166161.1		c.2600-61T>C		intron	N/A	NP_001159633.1
	PPP1R9A	NM_001166162.1		c.2600-61T>C		intron	N/A	NP_001159634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R9A	ENST00000433360.6	TSL:1 MANE Select	c.2666-61T>C		intron	N/A	ENSP00000405514.1
	PPP1R9A	ENST00000289495.7	TSL:1	c.2600-61T>C		intron	N/A	ENSP00000289495.7
	PPP1R9A	ENST00000456331.6	TSL:1	c.2600-61T>C		intron	N/A	ENSP00000402893.2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55897 AN: 151846 Hom.: 10980 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.420 AC: 597103 AN: 1421046 Hom.: 127352 AF XY: 0.419 AC XY: 295567 AN XY: 706250

African (AFR) AF: 0.223 AC: 7253 AN: 32552

American (AMR) AF: 0.336 AC: 14513 AN: 43156

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 13488 AN: 24666

East Asian (EAS) AF: 0.447 AC: 17525 AN: 39236

South Asian (SAS) AF: 0.326 AC: 26950 AN: 82586

European-Finnish (FIN) AF: 0.382 AC: 18959 AN: 49600

Middle Eastern (MID) AF: 0.445 AC: 2231 AN: 5010

European-Non Finnish (NFE) AF: 0.435 AC: 471753 AN: 1085542

Other (OTH) AF: 0.416 AC: 24431 AN: 58698

GnomAD4 genome AF: 0.368 AC: 55906 AN: 151962 Hom.: 10979 Cov.: 31 AF XY: 0.365 AC XY: 27133 AN XY: 74276

African (AFR) AF: 0.231 AC: 9563 AN: 41472

American (AMR) AF: 0.378 AC: 5771 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2059 AN: 5136

South Asian (SAS) AF: 0.321 AC: 1546 AN: 4810

European-Finnish (FIN) AF: 0.371 AC: 3922 AN: 10558

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29553 AN: 67940

Other (OTH) AF: 0.422 AC: 890 AN: 2108

Alfa AF: 0.416 Hom.: 17904

Bravo AF: 0.366

Asia WGS AF: 0.340 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.64
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs854522; hg19: chr7-94897801; COSMIC: COSV56888179;