chr3-188609167-A-G

Position:

• chr3-188609167-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375462.1(LPP):​c.436A>G​(p.Thr146Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00983 in 1,600,794 control chromosomes in the GnomAD database, including 1,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.052 (655 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (612 hom.)
• Consequence: LPP NM_001375462.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.239

Genes affected

LPP (HGNC:6679): (LIM domain containing preferred translocation partner in lipoma) This gene encodes a member of a subfamily of LIM domain proteins that are characterized by an N-terminal proline-rich region and three C-terminal LIM domains. The encoded protein localizes to the cell periphery in focal adhesions and may be involved in cell-cell adhesion and cell motility. This protein also shuttles through the nucleus and may function as a transcriptional co-activator. This gene is located at the junction of certain disease-related chromosomal translocations, which result in the expression of chimeric proteins that may promote tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

LOC124906316 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012661517).
• BP6: Variant 3-188609167-A-G is Benign according to our data. Variant chr3-188609167-A-G is described in ClinVar as [Benign]. Clinvar id is 1280879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.436A>G	p.Thr146Ala	missense_variant	7/12	ENST00000617246.5
LOC124906316	XR_007096213.1	n.496-1397T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.436A>G	p.Thr146Ala	missense_variant	7/12	1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7838 AN: 151598 Hom.: 653 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0312

GnomAD3 exomes AF: 0.0136 AC: 3324 AN: 244584 Hom.: 267 AF XY: 0.0101 AC XY: 1330 AN XY: 132214

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.00931

Gnomad ASJ exome AF: 0.00277

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000304

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000704

Gnomad OTH exome AF: 0.00576

GnomAD4 exome AF: 0.00543 AC: 7873 AN: 1449080 Hom.: 612 Cov.: 31 AF XY: 0.00471 AC XY: 3387 AN XY: 719386

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000434

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000433

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0518 AC: 7861 AN: 151714 Hom.: 655 Cov.: 32 AF XY: 0.0506 AC XY: 3747 AN XY: 74122

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0309

Alfa AF: 0.0102 Hom.: 208

Bravo AF: 0.0596

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.177 AC: 779

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.0168 AC: 2036

Asia WGS AF: 0.0110 AC: 40 AN: 3478

EpiCase AF: 0.000819

EpiControl AF: 0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.024
DANN	Benign	0.60
DEOGEN2	Benign	0.0045	T;.;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.47	T;T;T;.;T
MetaRNN	Benign	0.0013	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.46	.;.;.;N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.25	N;N;.;.;.
REVEL	Benign	0.069
Sift	Benign	0.78	T;T;.;.;.
Sift4G	Benign	0.60	T;T;T;.;T
Polyphen		0.0	B;.;.;B;B
Vest4		0.047
ClinPred		0.0028	T
GERP RS		-2.5
Varity_R		0.025
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs35417432; hg19: chr3-188326955;