NM_002504.6:c.947C>T

Variant names:

• chr9-33295341-C-T
• NM_002504.6:c.947C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002504.6(NFX1):​c.947C>T​(p.Thr316Ile) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFX1 NM_002504.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.476
• Publications: 0 publications found

Genes affected

NFX1 (HGNC:7803): (nuclear transcription factor, X-box binding 1) MHC class II gene expression is controlled primarily at the transcriptional level by transcription factors that bind to the X and Y boxes, two highly conserved elements in the proximal promoter of MHC class II genes. The protein encoded by this gene is a transcriptional repressor capable of binding to the conserved X box motif of HLA-DRA and other MHC class II genes in vitro. The protein may play a role in regulating the duration of an inflammatory response by limiting the period in which class II MHC molecules are induced by IFN-gamma. Three alternative splice variants, each of which encodes a different isoform, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054630786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002504.6. 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
	NFX1	NM_002504.6	MANE Select	c.947C>T	p.Thr316Ile	missense	Exon 2 of 24	NP_002495.2
	NFX1	NM_001318758.2		c.947C>T	p.Thr316Ile	missense	Exon 2 of 24	NP_001305687.1
	NFX1	NM_147134.4		c.947C>T	p.Thr316Ile	missense	Exon 2 of 16	NP_667345.1	Q12986-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFX1	ENST00000379540.8	TSL:1 MANE Select	c.947C>T	p.Thr316Ile	missense	Exon 2 of 24	ENSP00000368856.3	Q12986-1
	NFX1	ENST00000318524.6	TSL:1	c.947C>T	p.Thr316Ile	missense	Exon 2 of 16	ENSP00000317695.6	Q12986-3
	NFX1	ENST00000379521.8	TSL:1	n.1008C>T		non_coding_transcript_exon	Exon 2 of 21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.48
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.066
Sift	Benign	0.26	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.058
MutPred		0.27		Loss of phosphorylation at T316 (P = 0.0657)
MVP		0.34
MPC		0.21
ClinPred		0.051	T
GERP RS		4.0
Varity_R		0.043
gMVP		0.29
Mutation Taster		=90/10	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: chr9-33295339;