NM_001365902.3:c.1140G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Malan overgrowth syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Orphanet
• Marshall-Smith syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000279044 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 198780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.233 with no splicing effect.
• BS2: High AC in GnomAd4 at 356 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365902.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	NM_001365902.3	MANE Select	c.1140G>A	p.Ser380Ser	synonymous	Exon 8 of 11	NP_001352831.1	Q14938-1
	NFIX	NM_001378405.1		c.1188G>A	p.Ser396Ser	synonymous	Exon 8 of 11	NP_001365334.1
	NFIX	NM_001271043.2		c.1164G>A	p.Ser388Ser	synonymous	Exon 8 of 11	NP_001257972.1	B4DHW2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	ENST00000592199.6	TSL:5 MANE Select	c.1140G>A	p.Ser380Ser	synonymous	Exon 8 of 11	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000587260.1	TSL:1	c.1137G>A	p.Ser379Ser	synonymous	Exon 7 of 9	ENSP00000467785.1	Q14938-5
	NFIX	ENST00000587760.5	TSL:1	c.1116G>A	p.Ser372Ser	synonymous	Exon 8 of 10	ENSP00000466389.1	Q14938-6

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

GnomAD2 exomes AF: 0.00228 AC: 568 AN: 249118 AF XY: 0.00222

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 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

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.00315 AC: 141 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 22 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00101 AC: 87 AN: 86258

European-Finnish (FIN) AF: 0.00174 AC: 93 AN: 53374

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00351 AC: 3904 AN: 1111860

Other (OTH) AF: 0.00262 AC: 158 AN: 60370

GnomAD4 genome AF: 0.00234 AC: 356 AN: 152204 Hom.: 1 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74430

African (AFR) AF: 0.000602 AC: 25 AN: 41516

American (AMR) AF: 0.00301 AC: 46 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4818

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00347 AC: 236 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Marshall-Smith syndrome;C3553660:Malan overgrowth syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		0.23
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs201174259; hg19: chr19-13192555;