1-61082806-CTG-C

Position:

• chr1-61082806-CTG-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001134673.4(NFIA):​c.17_18delGT​(p.Cys6fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. C6C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 28)
• Consequence: NFIA NM_001134673.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.63

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 38 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-61082806-CTG-C is Pathogenic according to our data. Variant chr1-61082806-CTG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3344300.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.17_18delGT	p.Cys6fs	frameshift_variant	1/11	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.152_153delGT	p.Cys51fs	frameshift_variant	2/12		NP_001138984.1
NFIA	NM_005595.5	c.17_18delGT	p.Cys6fs	frameshift_variant	1/10		NP_005586.1
NFIA	NM_001145511.2	c.3+5180_3+5181delGT		intron_variant			NP_001138983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.17_18delGT	p.Cys6fs	frameshift_variant	1/11	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes Cov.: 28

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

GnomAD4 genome Cov.: 28

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

NFIA-related disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2024

The NFIA c.17_18delGT variant is predicted to result in a frameshift and premature protein termination (p.Cys6Serfs*5). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Frameshift variants in NFIA are expected to be pathogenic. This variant is interpreted as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-61548478;