4-122922374-C-T

Variant names:

• chr4-122922374-C-T
• rs758997886
• NM_007083.5:c.199G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007083.5(NUDT6):​c.199G>A​(p.Asp67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,454,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: NUDT6 NM_007083.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120229095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007083.5. 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
	NUDT6	NM_007083.5	MANE Select	c.199G>A	p.Asp67Asn	missense	Exon 1 of 5	NP_009014.2
	NUDT6	NM_198041.3		c.-270+427G>A		intron	N/A	NP_932158.1	P53370-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT6	ENST00000304430.10	TSL:1 MANE Select	c.199G>A	p.Asp67Asn	missense	Exon 1 of 5	ENSP00000306070.5	P53370-1
	NUDT6	ENST00000339154.6	TSL:1	c.-270+427G>A		intron	N/A	ENSP00000344011.2	P53370-2
	NUDT6	ENST00000510735.1	TSL:5	c.67G>A	p.Asp23Asn	missense	Exon 1 of 3	ENSP00000423745.1	H0Y9C0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000870 AC: 2 AN: 229968 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1454074 Hom.: 0 Cov.: 29 AF XY: 0.00000691 AC XY: 5 AN XY: 723528

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000698 AC: 6 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111440

Other (OTH) AF: 0.0000166 AC: 1 AN: 60212

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000249 AC: 3

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	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.039
Sift	Benign	0.61	T
Sift4G	Benign	0.24	T
Polyphen		0.16	B
Vest4		0.35
MutPred		0.41		Gain of MoRF binding (P = 0.0511)
MVP		0.45
MPC		0.11
ClinPred		0.17	T
GERP RS		2.9
PromoterAI		-0.0075	Neutral
Varity_R		0.11
gMVP		0.26
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758997886; hg19: chr4-123843529;