chr16-4693872-C-T

Variant names:

• chr16-4693872-C-T
• rs1383997136
• NM_032349.4:c.146C>T

Variant summary

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

The NM_032349.4(NUDT16L1):​c.146C>T​(p.Ser49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (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: 3.13
• 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=0.31759804).

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.146C>T	p.Ser49Leu	missense	Exon 1 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001370585.1		c.146C>T	p.Ser49Leu	missense	Exon 1 of 3	NP_001357514.1
	NUDT16L1	NM_001193452.1		c.146C>T	p.Ser49Leu	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.146C>T	p.Ser49Leu	missense	Exon 1 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.146C>T	p.Ser49Leu	missense	Exon 1 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000590460.1	TSL:3	c.110C>T	p.Ser37Leu	missense	Exon 1 of 3	ENSP00000464821.1	K7EIN2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000637 AC: 1 AN: 156872 AF XY: 0.0000113

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: 0.0000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1392652 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 691622

African (AFR) AF: 0.00 AC: 0 AN: 28752

American (AMR) AF: 0.00 AC: 0 AN: 36518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24420

East Asian (EAS) AF: 0.00 AC: 0 AN: 32704

South Asian (SAS) AF: 0.00 AC: 0 AN: 78878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085638

Other (OTH) AF: 0.00 AC: 0 AN: 57680

GnomAD4 genome Cov.: 33

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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.092
Sift	Benign	0.063	T
Sift4G	Benign	0.39	T
Polyphen		0.93	P
Vest4		0.49
MutPred		0.30		Loss of MoRF binding (P = 0.1448)
MVP		0.51
MPC		1.0
ClinPred		0.91	D
GERP RS		3.8
PromoterAI		-0.048	Neutral
Varity_R		0.48
gMVP		0.56

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: rs1383997136; hg19: chr16-4743873; COSMIC: COSV105100574; COSMIC: COSV105100574;