1-61088234-GA-AG

Variant names:

• chr1-61088234-GA-AG
• NM_001134673.4:c.113_114delGAinsAG
• NFIA p.Arg38Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001134673.4(NFIA):​c.113_114delGAinsAG​(p.Arg38Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NFIA NM_001134673.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

NFIA (HGNC:7784): (nuclear factor I A) This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

NFIA Gene-Disease associations (from GenCC):

• brain malformations with or without urinary tract defects

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• chromosome 1p32-p31 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134673.4. 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
	NFIA	NM_001134673.4	MANE Select	c.113_114delGAinsAG	p.Arg38Gln	missense	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.248_249delGAinsAG	p.Arg83Gln	missense	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.89_90delGAinsAG	p.Arg30Gln	missense	N/A	NP_001138983.1	Q12857-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.113_114delGAinsAG	p.Arg38Gln	missense	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.113_114delGAinsAG	p.Arg38Gln	missense	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.248_249delGAinsAG	p.Arg83Gln	missense	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-61553906;