dbSNP rs35952068: NFIC:p.Thr265Ser (chr19-3434361-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001245002.2(NFIC):c.794C>G(p.Thr265Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000819 in 1,613,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 0 hom. )

Consequence

NFIC
NM_001245002.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033168375).

BS2

High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIC	NM_001245002.2 link	c.794C>G	p.Thr265Ser	missense_variant	Exon 5 of 11	ENST00000443272.3	NP_001231931.1	P08651-1B7Z4T6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIC	ENST00000443272.3 link	c.794C>G	p.Thr265Ser	missense_variant	Exon 5 of 11	2	NM_001245002.2	ENSP00000396843.2		P08651-1

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000484

AC:

121

AN:

250062

Hom.:

AF XY:

0.000577

AC XY:

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000892

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.000836

AC:

1222

AN:

1461078

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

582

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152308

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000776

Hom.:

Bravo

AF:

0.000627

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000552

AC:

EpiCase

AF:

0.00153

EpiControl

AF:

0.00154

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.767C>G (p.T256S) alteration is located in exon 1 (coding exon 1) of the NFIC gene. This alteration results from a C to G substitution at nucleotide position 767, causing the threonine (T) at amino acid position 256 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.056

.;.;.;.;.;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.033

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;.;.;.;L;L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.34

.;.;N;.;N;.;N

REVEL

Benign

0.099

Sift

Benign

0.16

.;.;T;.;T;.;T

Sift4G

Benign

0.77

.;T;T;T;T;T;T

Polyphen

0.082, 0.14, 0.20

.;B;B;.;B;.;B

Vest4

0.47, 0.46, 0.45, 0.44, 0.43, 0.46

MutPred

0.41

.;.;.;.;Gain of glycosylation at T265 (P = 0.0323);Gain of glycosylation at T265 (P = 0.0323);Gain of glycosylation at T265 (P = 0.0323);

MVP

0.34

MPC

0.64

ClinPred

0.018

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over