16-4695014-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032349.4(NUDT16L1):​c.471C>A​(p.Phe157Leu) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDT16L1 NM_032349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.06

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06428665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT16L1	NM_032349.4	c.471C>A	p.Phe157Leu	missense_variant	Exon 3 of 3	ENST00000304301.11	NP_115725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT16L1	ENST00000304301.11	c.471C>A	p.Phe157Leu	missense_variant	Exon 3 of 3	1	NM_032349.4	ENSP00000306670.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.471C>A (p.F157L) alteration is located in exon 3 (coding exon 3) of the NUDT16L1 gene. This alteration results from a C to A substitution at nucleotide position 471, causing the phenylalanine (F) at amino acid position 157 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.4
DANN	Benign	0.90
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.25
MutPred		0.32		Gain of methylation at R153 (P = 0.2714);
MVP		0.15
MPC		0.68
ClinPred		0.038	T
GERP RS		-8.4
Varity_R		0.18
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs139828708; hg19: chr16-4745015;