NM_007083.5:c.764C>G

Variant names:

• chr4-122893015-G-C
• rs138619142
• NM_007083.5:c.764C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007083.5(NUDT6):​c.764C>G​(p.Ala255Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUDT6 NM_007083.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

NUDT6 (HGNC:8053): (nudix hydrolase 6) This gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

FGF2 (HGNC:3676): (fibroblast growth factor 2) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2459966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT6	NM_007083.5	c.764C>G	p.Ala255Gly	missense_variant	Exon 5 of 5	ENST00000304430.10	NP_009014.2
FGF2	NM_001361665.2	c.*619G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000644866.2	NP_001348594.1
NUDT6	NM_198041.3	c.257C>G	p.Ala86Gly	missense_variant	Exon 5 of 5		NP_932158.1
FGF2	NM_002006.6	c.*619G>C		3_prime_UTR_variant	Exon 3 of 3		NP_001997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT6	ENST00000304430.10	c.764C>G	p.Ala255Gly	missense_variant	Exon 5 of 5	1	NM_007083.5	ENSP00000306070.5
FGF2	ENST00000644866.2	c.*619G>C		3_prime_UTR_variant	Exon 3 of 3		NM_001361665.2	ENSP00000494222.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.75	T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.90	P;.;.
Vest4		0.098
MutPred		0.58		Gain of glycosylation at T257 (P = 0.0489);.;.;
MVP		0.37
MPC		0.26
ClinPred		0.97	D
GERP RS		-3.6
Varity_R		0.82
gMVP		0.44

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

Other links and lift over

dbSNP: rs138619142; hg19: chr4-123814170;