16-4694153-C-A

Variant names:

• chr16-4694153-C-A
• rs2079482877
• NM_032349.4:c.329C>A

Variant summary

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

The NM_032349.4(NUDT16L1):​c.329C>A​(p.Ala110Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,433,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A110V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NUDT16L1 NM_032349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.329C>A	p.Ala110Glu	missense	Exon 2 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001370585.1		c.323C>A	p.Ala108Glu	missense	Exon 2 of 3	NP_001357514.1
	NUDT16L1	NM_001193452.1		c.329C>A	p.Ala110Glu	missense	Exon 2 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.329C>A	p.Ala110Glu	missense	Exon 2 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.329C>A	p.Ala110Glu	missense	Exon 2 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000860911.1		c.323C>A	p.Ala108Glu	missense	Exon 2 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433696 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 713516

African (AFR) AF: 0.00 AC: 0 AN: 31292

American (AMR) AF: 0.00 AC: 0 AN: 43824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 38032

South Asian (SAS) AF: 0.00 AC: 0 AN: 84898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106740

Other (OTH) AF: 0.00 AC: 0 AN: 59648

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.35	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.17
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.052	T
Polyphen		1.0	D
Vest4		0.91
MutPred		0.48		Gain of helix (P = 0.0325)
MVP		0.37
MPC		1.6
ClinPred		0.98	D
GERP RS		4.0
PromoterAI		0.031	Neutral
Varity_R		0.91
gMVP		0.87
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2079482877; hg19: chr16-4744154;