NM_014223.5:c.625C>G

Variant names:

• chr1-40762951-C-G
• NM_014223.5:c.625C>G

Variant summary

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

The NM_014223.5(NFYC):​c.625C>G​(p.Gln209Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NFYC NM_014223.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55
• Publications: 0 publications found

Genes affected

NFYC (HGNC:7806): (nuclear transcription factor Y subunit gamma) This gene encodes one subunit of a trimeric complex forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoters of a variety of genes. The encoded protein, subunit C, forms a tight dimer with the B subunit, a prerequisite for subunit A association. The resulting trimer binds to DNA with high specificity and affinity. Subunits B and C each contain a histone-like motif. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

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=0.34167704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014223.5. 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
	NFYC	NM_014223.5	MANE Select	c.625C>G	p.Gln209Glu	missense	Exon 7 of 10	NP_055038.2
	NFYC	NM_001308114.1		c.625C>G	p.Gln209Glu	missense	Exon 6 of 10	NP_001295043.1	Q13952-1
	NFYC	NM_001308115.2		c.625C>G	p.Gln209Glu	missense	Exon 7 of 10	NP_001295044.1	Q13952-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFYC	ENST00000447388.8	TSL:1 MANE Select	c.625C>G	p.Gln209Glu	missense	Exon 7 of 10	ENSP00000404427.3	Q13952-2
	NFYC	ENST00000308733.9	TSL:1	c.625C>G	p.Gln209Glu	missense	Exon 6 of 10	ENSP00000312617.5	Q13952-1
	NFYC	ENST00000372654.5	TSL:1	c.625C>G	p.Gln209Glu	missense	Exon 8 of 11	ENSP00000361738.1	Q13952-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.23
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.55	N
PhyloP100		7.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.81	P
Vest4		0.66
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0999)
MVP		0.61
MPC		1.9
ClinPred		0.87	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.28
Mutation Taster		=48/52	disease causing

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: chr1-41228623;