16-4693759-G-A

Variant names:

• chr16-4693759-G-A
• rs757999364
• NM_032349.4:c.33G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032349.4(NUDT16L1):​c.33G>A​(p.Gln11Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,407,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: NUDT16L1 NM_032349.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.128 with no splicing effect.

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.33G>A	p.Gln11Gln	synonymous	Exon 1 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001370585.1		c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 3	NP_001357514.1
	NUDT16L1	NM_001193452.1		c.33G>A	p.Gln11Gln	synonymous	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.33G>A	p.Gln11Gln	synonymous	Exon 1 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000860911.1		c.33G>A	p.Gln11Gln	synonymous	Exon 1 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000167 AC: 3 AN: 179868 AF XY: 0.00000997

Gnomad AFR exome AF: 0.000119

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000899

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 18 AN: 1407534 Hom.: 0 Cov.: 33 AF XY: 0.0000129 AC XY: 9 AN XY: 699096

African (AFR) AF: 0.00 AC: 0 AN: 29336

American (AMR) AF: 0.00 AC: 0 AN: 38612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24686

East Asian (EAS) AF: 0.00 AC: 0 AN: 33652

South Asian (SAS) AF: 0.00 AC: 0 AN: 80060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48368

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5540

European-Non Finnish (NFE) AF: 0.0000138 AC: 15 AN: 1089260

Other (OTH) AF: 0.0000345 AC: 2 AN: 58020

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.95
PhyloP100		-0.13
PromoterAI		-0.011	Neutral

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: rs757999364; hg19: chr16-4743760;