Variant chr4-105897932-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001033047.3(NPNT):c.103C>T(p.Leu35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,592 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 8 hom. )

Consequence

NPNT
NM_001033047.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

NPNT (HGNC:27405): (nephronectin) Predicted to enable integrin binding activity. Predicted to be involved in several processes, including cell-cell adhesion mediated by integrin; positive regulation of ERK1 and ERK2 cascade; and positive regulation of osteoblast differentiation. Predicted to act upstream of or within positive regulation of transforming growth factor beta receptor signaling pathway. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

NPNT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 4-105897932-C-T is Benign according to our data. Variant chr4-105897932-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655004.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPNT	NM_001033047.3 linkuse as main transcript	c.103C>T	p.Leu35=	synonymous_variant	2/12	ENST00000379987.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPNT	ENST00000379987.7 linkuse as main transcript	c.103C>T	p.Leu35=	synonymous_variant	2/12	1	NM_001033047.3		Q6UXI9-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

165

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00124

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00171

AC:

429

AN:

251198

Hom.:

AF XY:

0.00211

AC XY:

286

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00537

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00494

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00144

AC:

2102

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1140

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00477

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

152054

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.00124

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000732

Hom.:

Bravo

AF:

0.00101

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00214

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

NPNT: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over