rs201174259

Variant names:

• chr19-13081741-G-A
• rs201174259
• NM_001365902.3:c.1140G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-13081741-G-A
• chr19-13081741-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001365902.3(NFIX):​c.1140G>A​(p.Ser380Ser) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.233

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]

ENSG00000279044 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
NFIX	NM_001365902.3	c.1140G>A	p.Ser380Ser	synonymous_variant	Exon 8 of 11	ENST00000592199.6	NP_001352831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIX	ENST00000592199.6	c.1140G>A	p.Ser380Ser	synonymous_variant	Exon 8 of 11	5	NM_001365902.3	ENSP00000467512.1

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 356 AN: 152086 Hom.: 1 Cov.: 32

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.: 0 AF XY: 0.00222 AC XY: 300 AN XY: 135182

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.: 5 Cov.: 31 AF XY: 0.00298 AC XY: 2169 AN XY: 727122

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.: 1 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74430

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.: 1

Bravo AF: 0.00244

Asia WGS AF: 0.000577 AC: 2 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

Submissions by phenotype

not specified Benign:2

Jan 07, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NFIX: BP4, BP7 -

Marshall-Smith syndrome;C3553660:Malan overgrowth syndrome Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
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

Other links and lift over

dbSNP: rs201174259; hg19: chr19-13192555;