chr16-77735937-G-A

Variant names:

• chr16-77735937-G-A
• rs308925
• NM_001105663.3:c.299G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_001105663.3(NUDT7):​c.299G>A​(p.Arg100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,266 control chromosomes in the GnomAD database, including 30,743 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.18 (2686 hom., cov: 31)
  • Exomes 𝑓: 0.19 (28057 hom.)
• Consequence: NUDT7 NM_001105663.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 22 publications found

Genes affected

NUDT7 (HGNC:8054): (nudix hydrolase 7) The protein encoded by this gene is a member of the Nudix hydrolase family. Nudix hydrolases eliminate potentially toxic nucleotide metabolites from the cell and regulate the concentrations and availability of many different nucleotide substrates, cofactors, and signaling molecules. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.383857E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT7	NM_001105663.3	c.299G>A	p.Arg100His	missense_variant	Exon 3 of 4	ENST00000268533.9	NP_001099133.1
NUDT7	NM_001243657.2	c.299G>A	p.Arg100His	missense_variant	Exon 3 of 5		NP_001230586.1
NUDT7	NM_001243660.2	c.303+430G>A		intron_variant	Intron 3 of 3		NP_001230589.1
NUDT7	NM_001243661.2	c.190-5645G>A		intron_variant	Intron 2 of 2		NP_001230590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT7	ENST00000268533.9	c.299G>A	p.Arg100His	missense_variant	Exon 3 of 4	1	NM_001105663.3	ENSP00000268533.5

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27263 AN: 151844 Hom.: 2686 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.213 AC: 53105 AN: 249544 AF XY: 0.219

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.246

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.189 AC: 275657 AN: 1461304 Hom.: 28057 Cov.: 33 AF XY: 0.192 AC XY: 139783 AN XY: 726990

African (AFR) AF: 0.118 AC: 3955 AN: 33472

American (AMR) AF: 0.219 AC: 9807 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4925 AN: 26134

East Asian (EAS) AF: 0.280 AC: 11108 AN: 39690

South Asian (SAS) AF: 0.307 AC: 26446 AN: 86222

European-Finnish (FIN) AF: 0.265 AC: 14165 AN: 53414

Middle Eastern (MID) AF: 0.191 AC: 1102 AN: 5768

European-Non Finnish (NFE) AF: 0.173 AC: 192516 AN: 1111506

Other (OTH) AF: 0.193 AC: 11633 AN: 60376

GnomAD4 genome AF: 0.179 AC: 27264 AN: 151962 Hom.: 2686 Cov.: 31 AF XY: 0.186 AC XY: 13838 AN XY: 74258

African (AFR) AF: 0.122 AC: 5073 AN: 41494

American (AMR) AF: 0.209 AC: 3188 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1364 AN: 5144

South Asian (SAS) AF: 0.331 AC: 1590 AN: 4800

European-Finnish (FIN) AF: 0.274 AC: 2886 AN: 10532

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11992 AN: 67946

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.181 Hom.: 13047

Bravo AF: 0.168

TwinsUK AF: 0.175 AC: 650

ALSPAC AF: 0.173 AC: 666

ESP6500AA AF: 0.116 AC: 473

ESP6500EA AF: 0.168 AC: 1410

ExAC AF: 0.211 AC: 25513

Asia WGS AF: 0.304 AC: 1055 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0050
DANN	Benign	0.88
DEOGEN2	Benign	0.015	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.83	T;T;T
MetaRNN	Benign	0.00094	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.33	N;N;.
PhyloP100		-2.4
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.87	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.53	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0020	.;B;.
Vest4		0.015
MPC		0.016
ClinPred		0.0021	T
GERP RS		-3.4
Varity_R		0.093
gMVP		0.41
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs308925; hg19: chr16-77769834; COSMIC: COSV51746573; COSMIC: COSV51746573;