NM_152395.3:c.205C>G

Variant names:

• chr3-131382112-C-G
• rs150437674
• NM_152395.3:c.205C>G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_152395.3(NUDT16):​c.205C>G​(p.Leu69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,608,026 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (4 hom., cov: 33)
  • Exomes 𝑓: 0.010 (87 hom.)
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.85

Genes affected

NUDT16 (HGNC:26442): (nudix hydrolase 16) Enables several functions, including RNA binding activity; metal ion binding activity; and purine ribonucleoside triphosphate binding activity. Involved in IDP catabolic process; RNA metabolic process; and positive regulation of cell cycle process. Located in cytoplasm; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007732898).
• BP6: Variant 3-131382112-C-G is Benign according to our data. Variant chr3-131382112-C-G is described in ClinVar as [Benign]. Clinvar id is 783313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16	NM_152395.3	c.205C>G	p.Leu69Val	missense_variant	Exon 2 of 3	ENST00000521288.2	NP_689608.2
NUDT16	NM_001171906.2	c.205C>G	p.Leu69Val	missense_variant	Exon 2 of 2		NP_001165377.1
NUDT16	NM_001171905.2	c.67C>G	p.Leu23Val	missense_variant	Exon 2 of 4		NP_001165376.1
NUDT16	NR_033268.2	n.339C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT16	ENST00000521288.2	c.205C>G	p.Leu69Val	missense_variant	Exon 2 of 3	1	NM_152395.3	ENSP00000429274.2
NUDT16	ENST00000502852.1	c.205C>G	p.Leu69Val	missense_variant	Exon 2 of 2	2		ENSP00000422375.1
NUDT16	ENST00000537561.5	c.67C>G	p.Leu23Val	missense_variant	Exon 2 of 4	5		ENSP00000440230.1

Frequencies

GnomAD3 genomes AF: 0.00715 AC: 1089 AN: 152230 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00207

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.00866

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00794 AC: 1957 AN: 246414 Hom.: 12 AF XY: 0.00822 AC XY: 1099 AN XY: 133740

Gnomad AFR exome AF: 0.00232

Gnomad AMR exome AF: 0.00502

Gnomad ASJ exome AF: 0.0159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00435

Gnomad FIN exome AF: 0.00941

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00702

GnomAD4 exome AF: 0.0100 AC: 14568 AN: 1455678 Hom.: 87 Cov.: 32 AF XY: 0.00981 AC XY: 7098 AN XY: 723682

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00489

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00411

Gnomad4 FIN exome AF: 0.00951

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.00883

GnomAD4 genome AF: 0.00714 AC: 1088 AN: 152348 Hom.: 4 Cov.: 33 AF XY: 0.00664 AC XY: 495 AN XY: 74496

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00866

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0108 Hom.: 4

Bravo AF: 0.00676

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0106 AC: 91

ExAC AF: 0.00739 AC: 897

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 03, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D;D;D
MetaRNN	Benign	0.0077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.074	T;T;T
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.55
MVP		0.26
MPC		1.3
ClinPred		0.012	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.74

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: rs150437674; hg19: chr3-131100956; COSMIC: COSV99072591; COSMIC: COSV99072591;