10-120589457-C-T

Variant names:

• chr10-120589457-C-T
• rs1047369
• NM_001030059.3:c.771C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001030059.3(PLPP4):​c.771C>T​(p.Ser257Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,724 control chromosomes in the GnomAD database, including 42,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3095 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39877 hom.)
• Consequence: PLPP4 NM_001030059.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0260
• Publications: 12 publications found

Genes affected

PLPP4 (HGNC:23531): (phospholipid phosphatase 4) Enables diacylglycerol diphosphate phosphatase activity; identical protein binding activity; and phosphatidate phosphatase activity. Involved in phospholipid dephosphorylation and regulation of calcium ion import. Predicted to be located in plasma membrane. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 10-120589457-C-T is Benign according to our data. Variant chr10-120589457-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2549582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.026 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030059.3. 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
	PLPP4	NM_001030059.3	MANE Select	c.771C>T	p.Ser257Ser	synonymous	Exon 7 of 7	NP_001025230.1
	PLPP4	NM_001318167.2		c.582C>T	p.Ser194Ser	synonymous	Exon 5 of 5	NP_001305096.1
	PLPP4	NR_134516.1		n.635C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP4	ENST00000398250.6	TSL:1 MANE Select	c.771C>T	p.Ser257Ser	synonymous	Exon 7 of 7	ENSP00000381302.1
	PLPP4	ENST00000369073.3	TSL:5	n.741C>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29887 AN: 151994 Hom.: 3091 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.202 AC: 50375 AN: 249264 AF XY: 0.207

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.0607

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.229 AC: 335416 AN: 1461612 Hom.: 39877 Cov.: 33 AF XY: 0.230 AC XY: 167043 AN XY: 727114

African (AFR) AF: 0.148 AC: 4959 AN: 33478

American (AMR) AF: 0.183 AC: 8177 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3151 AN: 26134

East Asian (EAS) AF: 0.0549 AC: 2178 AN: 39700

South Asian (SAS) AF: 0.252 AC: 21750 AN: 86242

European-Finnish (FIN) AF: 0.208 AC: 11110 AN: 53416

Middle Eastern (MID) AF: 0.159 AC: 913 AN: 5752

European-Non Finnish (NFE) AF: 0.243 AC: 270037 AN: 1111798

Other (OTH) AF: 0.218 AC: 13141 AN: 60380

GnomAD4 genome AF: 0.197 AC: 29921 AN: 152112 Hom.: 3095 Cov.: 32 AF XY: 0.197 AC XY: 14637 AN XY: 74354

African (AFR) AF: 0.152 AC: 6304 AN: 41512

American (AMR) AF: 0.169 AC: 2588 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3468

East Asian (EAS) AF: 0.0644 AC: 332 AN: 5158

South Asian (SAS) AF: 0.241 AC: 1160 AN: 4816

European-Finnish (FIN) AF: 0.215 AC: 2276 AN: 10580

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16227 AN: 67980

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.210 Hom.: 6129

Bravo AF: 0.189

Asia WGS AF: 0.201 AC: 699 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 22, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		0.026
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: rs1047369; hg19: chr10-122348969; COSMIC: COSV64826655; COSMIC: COSV64826655;