chr3-131382112-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 783313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152395.3. 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
	NUDT16	NM_152395.3	MANE Select	c.205C>G	p.Leu69Val	missense	Exon 2 of 3	NP_689608.2	Q96DE0-1
	NUDT16	NM_001171906.2		c.205C>G	p.Leu69Val	missense	Exon 2 of 2	NP_001165377.1	Q96DE0-4
	NUDT16	NM_001171905.2		c.67C>G	p.Leu23Val	missense	Exon 2 of 4	NP_001165376.1	Q96DE0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT16	ENST00000521288.2	TSL:1 MANE Select	c.205C>G	p.Leu69Val	missense	Exon 2 of 3	ENSP00000429274.2	Q96DE0-1
	NUDT16	ENST00000502852.1	TSL:2	c.205C>G	p.Leu69Val	missense	Exon 2 of 2	ENSP00000422375.1	Q96DE0-4
	NUDT16	ENST00000537561.5	TSL:5	c.67C>G	p.Leu23Val	missense	Exon 2 of 4	ENSP00000440230.1	Q96DE0-3

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

GnomAD2 exomes AF: 0.00794 AC: 1957 AN: 246414 AF XY: 0.00822

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 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

African (AFR) AF: 0.00159 AC: 53 AN: 33268

American (AMR) AF: 0.00489 AC: 215 AN: 43934

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 420 AN: 25884

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39598

South Asian (SAS) AF: 0.00411 AC: 352 AN: 85744

European-Finnish (FIN) AF: 0.00951 AC: 499 AN: 52484

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5742

European-Non Finnish (NFE) AF: 0.0113 AC: 12480 AN: 1108972

Other (OTH) AF: 0.00883 AC: 530 AN: 60052

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

African (AFR) AF: 0.00207 AC: 86 AN: 41594

American (AMR) AF: 0.00582 AC: 89 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4834

European-Finnish (FIN) AF: 0.00866 AC: 92 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 722 AN: 68028

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.092
Sift	Benign	0.074	T
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.55
MVP		0.26
MPC		1.3
ClinPred		0.012	T
GERP RS		1.8
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.74
Mutation Taster		=61/39	polymorphism

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

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