19-13024113-CAAAAAAA-CAAAAAAAAAAAA

Variant names:

• chr19-13024113-C-CAAAAA
• rs113861190
• NM_001365902.3:c.28-895_28-891dupAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001365902.3(NFIX):​c.28-895_28-891dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000549 in 309,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.28-895_28-891dupAAAAA		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_001378404.1		c.3+92_3+96dupAAAAA		intron	N/A	NP_001365333.1	D2DXM9
	NFIX	NM_001440616.1		c.3+92_3+96dupAAAAA		intron	N/A	NP_001427545.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	ENST00000592199.6	TSL:5 MANE Select	c.28-908_28-907insAAAAA		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000587760.5	TSL:1	c.3+79_3+80insAAAAA		intron	N/A	ENSP00000466389.1	Q14938-6
	NFIX	ENST00000585575.5	TSL:5	c.3+79_3+80insAAAAA		intron	N/A	ENSP00000468794.1	Q14938-4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.0000549 AC: 17 AN: 309830 Hom.: 0 AF XY: 0.0000659 AC XY: 11 AN XY: 167008

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7262

American (AMR) AF: 0.00 AC: 0 AN: 10802

Ashkenazi Jewish (ASJ) AF: 0.000113 AC: 1 AN: 8848

East Asian (EAS) AF: 0.0000560 AC: 1 AN: 17842

South Asian (SAS) AF: 0.0000887 AC: 3 AN: 33806

European-Finnish (FIN) AF: 0.000130 AC: 2 AN: 15378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1262

European-Non Finnish (NFE) AF: 0.0000455 AC: 9 AN: 197922

Other (OTH) AF: 0.0000599 AC: 1 AN: 16708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113861190; hg19: chr19-13134927;