NM_198571.3:c.1045G>C

Variant names:

• chr7-101172144-C-G
• rs1797337346
• NM_198571.3:c.1045G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198571.3(NAT16):​c.1045G>C​(p.Val349Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAT16 NM_198571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.209
• Publications: 0 publications found

Genes affected

NAT16 (HGNC:22030): (N-acetyltransferase 16 (putative)) Predicted to enable acyltransferase activity, transferring groups other than amino-acyl groups. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02762127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198571.3. 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
	NAT16	NM_198571.3	MANE Select	c.1045G>C	p.Val349Leu	missense	Exon 4 of 4	NP_940973.2	Q8N8M0-1
	NAT16	NM_001369694.1		c.1045G>C	p.Val349Leu	missense	Exon 5 of 5	NP_001356623.1	Q8N8M0-1
	NAT16	NM_001369695.1		c.1045G>C	p.Val349Leu	missense	Exon 4 of 4	NP_001356624.1	Q8N8M0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT16	ENST00000300303.7	TSL:2 MANE Select	c.1045G>C	p.Val349Leu	missense	Exon 4 of 4	ENSP00000300303.2	Q8N8M0-1
	NAT16	ENST00000455377.5	TSL:1	c.1045G>C	p.Val349Leu	missense	Exon 5 of 5	ENSP00000395125.1	Q8N8M0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461792 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111948

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

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.21
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.037
Sift	Benign	0.34	T
Sift4G	Benign	0.38	T
Polyphen		0.0010	B
Vest4		0.035
MutPred		0.25		Loss of catalytic residue at V349 (P = 0.0386)
MVP		0.055
MPC		0.48
ClinPred		0.088	T
GERP RS		3.0
Varity_R		0.083
gMVP		0.10
Mutation Taster		=99/1	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: rs1797337346; hg19: chr7-100815425;