19-3381964-A-T

Variant names:

• chr19-3381964-A-T
• rs769248336
• NM_001245002.2:c.283A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001245002.2(NFIC):​c.283A>T​(p.Ser95Cys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S95G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NFIC NM_001245002.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32143715).

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.283A>T	p.Ser95Cys	missense	Exon 2 of 11	NP_001231931.1	P08651-1
	NFIC	NM_205843.3		c.256A>T	p.Ser86Cys	missense	Exon 2 of 11	NP_995315.1	P08651-2
	NFIC	NM_001245004.2		c.283A>T	p.Ser95Cys	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.283A>T	p.Ser95Cys	missense	Exon 2 of 11	ENSP00000396843.2	P08651-1
	NFIC	ENST00000589123.6	TSL:1	c.256A>T	p.Ser86Cys	missense	Exon 2 of 11	ENSP00000465655.1	P08651-2
	NFIC	ENST00000341919.8	TSL:1	c.283A>T	p.Ser95Cys	missense	Exon 2 of 9	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.51
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.38
Sift	Benign	0.12	T
Sift4G	Benign	0.085	T
Polyphen		0.43	B
Vest4		0.40
MutPred		0.61		Gain of sheet (P = 0.0477)
MVP		0.64
MPC		2.2
ClinPred		0.49	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.96
Mutation Taster		=50/50

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

dbSNP: rs769248336; hg19: chr19-3381962;