chr16-4695014-C-T

Variant names:

• chr16-4695014-C-T
• rs139828708
• NM_032349.4:c.471C>T

Variant summary

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

The NM_001193452.1(NUDT16L1):​c.541C>T​(p.Pro181Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/12 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. P181T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NUDT16L1 NM_001193452.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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=0.07390025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193452.1. 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.471C>T	p.Phe157Phe	synonymous	Exon 3 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001193452.1		c.541C>T	p.Pro181Ser	missense	Exon 3 of 3	NP_001180381.1	W4VSQ8
	NUDT16L1	NM_001370586.1		c.535C>T	p.Pro179Ser	missense	Exon 3 of 3	NP_001357515.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT16L1	ENST00000304301.11	TSL:1 MANE Select	c.471C>T	p.Phe157Phe	synonymous	Exon 3 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.*446C>T		3_prime_UTR	Exon 2 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000586536.1	TSL:2	c.541C>T	p.Pro181Ser	missense	Exon 3 of 3	ENSP00000468346.1	W4VSQ8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460690 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726758

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.8
DANN	Benign	0.94
DEOGEN2	Benign	0.0053	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.074	T
PhyloP100		-1.1
Sift4G	Pathogenic	0.0	D
Vest4		0.087
MVP		0.72
GERP RS		-8.4

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: rs139828708; hg19: chr16-4745015;