Genetic Variant NFIC:p.Val184Leu (chr19-3382231-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001245002.2(NFIC):c.550G>T(p.Val184Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NFIC
NM_001245002.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18

Publications

0 publications found

Variant links:

Genes affected

NFIC (HGNC:7786): (nuclear factor I C) The protein encoded by this gene belongs to the CTF/NF-I family. These are dimeric DNA-binding proteins, and function as cellular transcription factors and as replication factors for adenovirus DNA replication. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

NFIC links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27836874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001245002.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFIC	NM_001245002.2	MANE Select	c.550G>T	p.Val184Leu	missense	Exon 2 of 11	NP_001231931.1	P08651-1
NFIC	NM_205843.3		c.523G>T	p.Val175Leu	missense	Exon 2 of 11	NP_995315.1	P08651-2
NFIC	NM_001245004.2		c.550G>T	p.Val184Leu	missense	Exon 2 of 10	NP_001231933.1	P08651-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFIC	ENST00000443272.3	TSL:2 MANE Select	c.550G>T	p.Val184Leu	missense	Exon 2 of 11	ENSP00000396843.2	P08651-1
NFIC	ENST00000589123.6	TSL:1	c.523G>T	p.Val175Leu	missense	Exon 2 of 11	ENSP00000465655.1	P08651-2
NFIC	ENST00000341919.8	TSL:1	c.550G>T	p.Val184Leu	missense	Exon 2 of 9	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449474

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5404

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110774

Other (OTH)

AF:

0.00

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.027

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

4.2

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.15

Sift

Benign

0.091

Sift4G

Benign

0.18

Polyphen

0.068

Vest4

0.53

MutPred

0.50

Gain of helix (P = 0.0425)

MVP

0.62

MPC

0.50

ClinPred

0.46

GERP RS

1.4

Varity_R

0.028

gMVP

0.92

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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