Genetic Variant NM_001365902.3:c.28-904_28-891dupAAAAAAAAAAAAAA (chr19-13024113-C-CAAAAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001365902.3(NFIX):c.28-904_28-891dupAAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 309,860 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

NFIX
NM_001365902.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.632

Publications

0 publications found

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 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

NFIX links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFIX	NM_001365902.3	MANE Select	c.28-904_28-891dupAAAAAAAAAAAAAA	intron	N/A	NP_001352831.1	Q14938-1
NFIX	NM_001378404.1		c.3+83_3+96dupAAAAAAAAAAAAAA	intron	N/A	NP_001365333.1	D2DXM9
NFIX	NM_001440616.1		c.3+83_3+96dupAAAAAAAAAAAAAA	intron	N/A	NP_001427545.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000323

AC:

AN:

309860

Hom.:

AF XY:

0.00

AC XY:

AN XY:

167028

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

7266

American (AMR)

AF:

0.00

AC:

AN:

10802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8848

East Asian (EAS)

AF:

0.00

AC:

AN:

17846

South Asian (SAS)

AF:

0.00

AC:

AN:

33810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1262

European-Non Finnish (NFE)

AF:

0.00000505

AC:

AN:

197936

Other (OTH)

AF:

0.00

AC:

AN:

16710

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over