chr19-13023630-CTTTT-C

Variant names:

• chr19-13023630-CTTTT-C
• rs201731717
• NM_001365902.3:c.28-1379_28-1376delTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001365902.3(NFIX):​c.28-1379_28-1376delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000933 in 128,668 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000093 (0 hom., cov: 26)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 12 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.28-1379_28-1376delTTTT		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_002501.4		c.28-1379_28-1376delTTTT		intron	N/A	NP_002492.2	Q14938-3
	NFIX	NM_001365982.2		c.28-1379_28-1376delTTTT		intron	N/A	NP_001352911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	ENST00000592199.6	TSL:5 MANE Select	c.28-1390_28-1387delTTTT		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000397661.6	TSL:5	c.28-1390_28-1387delTTTT		intron	N/A	ENSP00000380781.2	Q14938-3
	NFIX	ENST00000590027.1	TSL:2	c.-114-1390_-114-1387delTTTT		intron	N/A	ENSP00000465616.1	K7EKH0

Frequencies

GnomAD3 genomes AF: 0.0000933 AC: 12 AN: 128668 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000778

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000149

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000933 AC: 12 AN: 128668 Hom.: 0 Cov.: 26 AF XY: 0.000113 AC XY: 7 AN XY: 61978

African (AFR) AF: 0.0000587 AC: 2 AN: 34060

American (AMR) AF: 0.0000778 AC: 1 AN: 12856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3092

East Asian (EAS) AF: 0.00 AC: 0 AN: 4332

South Asian (SAS) AF: 0.00 AC: 0 AN: 4006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.000149 AC: 9 AN: 60360

Other (OTH) AF: 0.00 AC: 0 AN: 1720

Alfa AF: 0.0000613 Hom.: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201731717; hg19: chr19-13134444;