16-4693763-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032349.4(NUDT16L1):​c.37A>C​(p.Ser13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,408,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. S13N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NUDT16L1 NM_032349.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29404485).

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>C	p.Ser13Arg	missense	Exon 1 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001370585.1		c.37A>C	p.Ser13Arg	missense	Exon 1 of 3	NP_001357514.1
	NUDT16L1	NM_001193452.1		c.37A>C	p.Ser13Arg	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>C	p.Ser13Arg	missense	Exon 1 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.37A>C	p.Ser13Arg	missense	Exon 1 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000860911.1		c.37A>C	p.Ser13Arg	missense	Exon 1 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000213 AC: 3 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: 0.00000275 AC: 3 AN: 1089808

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.083
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.72	T
PhyloP100		1.6
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.041	D
Sift4G	Benign	0.092	T
Polyphen		0.78	P
Vest4		0.28
MutPred		0.24		Gain of helix (P = 0.027)
MVP		0.77
MPC		1.2
ClinPred		0.91	D
GERP RS		4.9
PromoterAI		0.027	Neutral
Varity_R		0.68
gMVP		0.77
Mutation Taster		=59/41	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: rs748039368; hg19: chr16-4743764;