19-3381988-G-T

Variant names:

• chr19-3381988-G-T
• NM_001245002.2:c.307G>T

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.307G>T​(p.Gly103Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G103G) has been classified 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: 3.58
• 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=0.22673202).

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.307G>T	p.Gly103Cys	missense	Exon 2 of 11	NP_001231931.1	P08651-1
	NFIC	NM_205843.3		c.280G>T	p.Gly94Cys	missense	Exon 2 of 11	NP_995315.1	P08651-2
	NFIC	NM_001245004.2		c.307G>T	p.Gly103Cys	missense	Exon 2 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.307G>T	p.Gly103Cys	missense	Exon 2 of 11	ENSP00000396843.2	P08651-1
	NFIC	ENST00000589123.6	TSL:1	c.280G>T	p.Gly94Cys	missense	Exon 2 of 11	ENSP00000465655.1	P08651-2
	NFIC	ENST00000341919.8	TSL:1	c.307G>T	p.Gly103Cys	missense	Exon 2 of 9	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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	0.072
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.57
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-1.7	N
PhyloP100		3.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	5.7	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0030	B
Vest4		0.20
MutPred		0.73		Gain of catalytic residue at P102 (P = 0.0054)
MVP		0.24
MPC		1.4
ClinPred		0.70	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.94
Mutation Taster		=79/21	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: chr19-3381986;