rs1553182964

chr1-61404169-CCTTA-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_001134673.4(NFIA):c.1145_1148del(p.Tyr382SerfsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFIA NM_001134673.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.91

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 1-61404169-CCTTA-C is Pathogenic according to our data. Variant chr1-61404169-CCTTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 521252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIA	NM_001134673.4	c.1145_1148del	p.Tyr382SerfsTer14	frameshift_variant	8/11	ENST00000403491.8
NFIA	NM_001145511.2	c.1121_1124del	p.Tyr374SerfsTer14	frameshift_variant	8/11
NFIA	NM_001145512.2	c.1280_1283del	p.Tyr427SerfsTer14	frameshift_variant	9/12
NFIA	NM_005595.5	c.1145_1148del	p.Tyr382SerfsTer14	frameshift_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIA	ENST00000403491.8	c.1145_1148del	p.Tyr382SerfsTer14	frameshift_variant	8/11	1	NM_001134673.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2016

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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

LitVar

Other links and lift over

dbSNP: rs1553182964; hg19: chr1-61869841;