rs576393185

Variant names:

• chr3-131381817-C-A
• rs576393185
• NM_152395.3:c.13C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-131381817-C-A
• chr3-131381817-C-G
• chr3-131381817-C-T

Variant summary

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

The NM_152395.3(NUDT16):​c.13C>A​(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NUDT16 NM_152395.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 1 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]

NUDT16-DT (HGNC:27947): (NUDT16 divergent transcript)

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=0.18385834).

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.13C>A	p.Arg5Ser	missense	Exon 1 of 3	NP_689608.2	Q96DE0-1
	NUDT16	NM_001171906.2		c.13C>A	p.Arg5Ser	missense	Exon 1 of 2	NP_001165377.1	Q96DE0-4
	NUDT16	NM_001171905.2		c.-1+72C>A		intron	N/A	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.13C>A	p.Arg5Ser	missense	Exon 1 of 3	ENSP00000429274.2	Q96DE0-1
	NUDT16	ENST00000502852.1	TSL:2	c.13C>A	p.Arg5Ser	missense	Exon 1 of 2	ENSP00000422375.1	Q96DE0-4
	NUDT16	ENST00000537561.5	TSL:5	c.-1+72C>A		intron	N/A	ENSP00000440230.1	Q96DE0-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000569 AC: 1 AN: 175820 AF XY: 0.00

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: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701068

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32522

American (AMR) AF: 0.00 AC: 0 AN: 38792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 37464

South Asian (SAS) AF: 0.00 AC: 0 AN: 82714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4142

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094588

Other (OTH) AF: 0.00 AC: 0 AN: 58786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	10
DANN	Benign	0.88
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.14
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.083
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.067	T
Vest4		0.20
MutPred		0.22		Gain of loop (P = 0.0502)
MVP		0.23
MPC		0.48
ClinPred		0.28	T
GERP RS		2.8
PromoterAI		-0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.66
gMVP		0.89
Mutation Taster		=89/11	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: rs576393185; hg19: chr3-131100661;