Variant 19-13081741-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001365902.3(NFIX):c.1140G>A(p.Ser380=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,872 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 5 hom. )

Consequence

NFIX
NM_001365902.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.233

Variant links:

Genes affected

NFIX (HGNC:7788): (nuclear factor I X) The protein encoded by this gene is a transcription factor that binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3 in viral and cellular promoters. The encoded protein can also stimulate adenovirus replication in vitro. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

NFIX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 19-13081741-G-A is Benign according to our data. Variant chr19-13081741-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13081741-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.233 with no splicing effect.

BS2

High AC in GnomAd4 at 356 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIX	NM_001365902.3 linkuse as main transcript	c.1140G>A	p.Ser380=	synonymous_variant	8/11	ENST00000592199.6	NP_001352831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIX	ENST00000592199.6 linkuse as main transcript	c.1140G>A	p.Ser380=	synonymous_variant	8/11	5	NM_001365902.3	ENSP00000467512	P4	Q14938-1

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00228

AC:

568

AN:

249118

Hom.:

AF XY:

0.00222

AC XY:

300

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00302

AC:

4417

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2169

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00351

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.00234

AC:

356

AN:

152204

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00244

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00284

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 07, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 27, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	NFIX: BP4, BP7, BS1 -

Marshall-Smith syndrome;C3553660:Malan overgrowth syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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