NM_001245002.2:c.894T>G

Variant names:

• chr19-3435143-T-G
• NM_001245002.2:c.894T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001245002.2(NFIC):​c.894T>G​(p.Asp298Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFIC NM_001245002.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.483
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09355658).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	NM_001245002.2	MANE Select	c.894T>G	p.Asp298Glu	missense	Exon 6 of 11	NP_001231931.1	P08651-1
	NFIC	NM_205843.3		c.867T>G	p.Asp289Glu	missense	Exon 6 of 11	NP_995315.1	P08651-2
	NFIC	NM_001245004.2		c.894T>G	p.Asp298Glu	missense	Exon 6 of 10	NP_001231933.1	P08651-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	ENST00000443272.3	TSL:2 MANE Select	c.894T>G	p.Asp298Glu	missense	Exon 6 of 11	ENSP00000396843.2	P08651-1
	NFIC	ENST00000589123.6	TSL:1	c.867T>G	p.Asp289Glu	missense	Exon 6 of 11	ENSP00000465655.1	P08651-2
	NFIC	ENST00000341919.8	TSL:1	c.894T>G	p.Asp298Glu	missense	Exon 6 of 9	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.44	N
PhyloP100		0.48
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.040
Sift	Benign	0.63	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.39		Gain of sheet (P = 0.0827)
MVP		0.19
MPC		0.46
ClinPred		0.23	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.092
Mutation Taster		=89/11	polymorphism

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

hg19: chr19-3435141;