rs141042248

Variant names:

• chr16-4695145-A-C
• rs141042248
• NM_032349.4:c.602A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032349.4(NUDT16L1):​c.602A>C​(p.Lys201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,074 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K201E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (6 hom.)
• Consequence: NUDT16L1 NM_032349.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 4 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01125443).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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.602A>C	p.Lys201Thr	missense	Exon 3 of 3	NP_115725.1	Q9BRJ7-1
	NUDT16L1	NM_001370585.1		c.596A>C	p.Lys199Thr	missense	Exon 3 of 3	NP_001357514.1
	NUDT16L1	NM_001370587.1		c.482A>C	p.Lys161Thr	missense	Exon 3 of 3	NP_001357516.1	K7ENA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT16L1	ENST00000304301.11	TSL:1 MANE Select	c.602A>C	p.Lys201Thr	missense	Exon 3 of 3	ENSP00000306670.5	Q9BRJ7-1
	NUDT16L1	ENST00000405142.1	TSL:1	c.*577A>C		3_prime_UTR	Exon 2 of 2	ENSP00000458144.1	Q9BRJ7-2
	NUDT16L1	ENST00000860911.1		c.596A>C	p.Lys199Thr	missense	Exon 3 of 3	ENSP00000530970.1

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 223 AN: 151984 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00106 AC: 265 AN: 250860 AF XY: 0.00110

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00158

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00159 AC: 2317 AN: 1460972 Hom.: 6 Cov.: 33 AF XY: 0.00151 AC XY: 1097 AN XY: 726818

African (AFR) AF: 0.00108 AC: 36 AN: 33480

American (AMR) AF: 0.000470 AC: 21 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26134

East Asian (EAS) AF: 0.000856 AC: 34 AN: 39700

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86258

European-Finnish (FIN) AF: 0.0000571 AC: 3 AN: 52558

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.00180 AC: 2004 AN: 1111972

Other (OTH) AF: 0.00232 AC: 140 AN: 60386

GnomAD4 genome AF: 0.00147 AC: 223 AN: 152102 Hom.: 1 Cov.: 32 AF XY: 0.00147 AC XY: 109 AN XY: 74340

African (AFR) AF: 0.00149 AC: 62 AN: 41474

American (AMR) AF: 0.000785 AC: 12 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5146

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00184 AC: 125 AN: 67996

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000749 Hom.: 0

Bravo AF: 0.00152

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000980 AC: 119

EpiCase AF: 0.00196

EpiControl AF: 0.00148

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	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.099
Sift	Benign	0.12	T
Sift4G	Benign	0.27	T
Polyphen		0.17	B
Vest4		0.46
MVP		0.31
MPC		0.68
ClinPred		0.026	T
GERP RS		4.4
Varity_R		0.27
gMVP		0.57
Mutation Taster		=93/7	polymorphism

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: rs141042248; hg19: chr16-4745146; COSMIC: COSV99275222; COSMIC: COSV99275222;