NM_032349.4:c.37A>G

Variant names:

• chr16-4693763-A-G
• rs748039368
• NM_032349.4:c.37A>G

Variant summary

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

The NM_032349.4(NUDT16L1):​c.37A>G​(p.Ser13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S13N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUDT16L1 NM_032349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

NUDT16L1 (HGNC:28154): (nudix hydrolase 16 like 1) Enables snoRNA binding activity. Involved in negative regulation of double-strand break repair via nonhomologous end joining. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18843937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032349.4. 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
	NUDT16L1	NM_032349.4	MANE Select	c.37A>G	p.Ser13Gly	missense	Exon 1 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001370585.1		c.37A>G	p.Ser13Gly	missense	Exon 1 of 3	NP_001357514.1
	NUDT16L1	NM_001193452.1		c.37A>G	p.Ser13Gly	missense	Exon 1 of 3	NP_001180381.1	W4VSQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT16L1	ENST00000304301.11	TSL:1 MANE Select	c.37A>G	p.Ser13Gly	missense	Exon 1 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.37A>G	p.Ser13Gly	missense	Exon 1 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000860911.1		c.37A>G	p.Ser13Gly	missense	Exon 1 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151962 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181530 AF XY: 0.00000987

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000887

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1408648 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 699716

African (AFR) AF: 0.00 AC: 0 AN: 29332

American (AMR) AF: 0.00 AC: 0 AN: 38798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24720

East Asian (EAS) AF: 0.00 AC: 0 AN: 33772

South Asian (SAS) AF: 0.00 AC: 0 AN: 80186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089808

Other (OTH) AF: 0.00 AC: 0 AN: 58062

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000838 AC: 1

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	0.093
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.87	T
PhyloP100		1.6
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.056
Sift	Benign	0.081	T
Sift4G	Benign	0.099	T
Polyphen		0.010	B
Vest4		0.42
MVP		0.74
MPC		0.61
ClinPred		0.20	T
GERP RS		4.9
PromoterAI		0.057	Neutral
Varity_R		0.53
gMVP		0.67

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: rs748039368; hg19: chr16-4743764;