7-101172144-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

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=0.02762127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT16	NM_198571.3	c.1045G>C	p.Val349Leu	missense_variant	Exon 4 of 4	ENST00000300303.7	NP_940973.2
NAT16	NM_001369694.1	c.1045G>C	p.Val349Leu	missense_variant	Exon 5 of 5		NP_001356623.1
NAT16	NM_001369695.1	c.1045G>C	p.Val349Leu	missense_variant	Exon 4 of 4		NP_001356624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT16	ENST00000300303.7	c.1045G>C	p.Val349Leu	missense_variant	Exon 4 of 4	2	NM_198571.3	ENSP00000300303.2
NAT16	ENST00000455377.5	c.1045G>C	p.Val349Leu	missense_variant	Exon 5 of 5	1		ENSP00000395125.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1045G>C (p.V349L) alteration is located in exon 4 (coding exon 3) of the NAT16 gene. This alteration results from a G to C substitution at nucleotide position 1045, causing the valine (V) at amino acid position 349 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	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;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;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.24	N;N
REVEL	Benign	0.037
Sift	Benign	0.34	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0010	B;B
Vest4		0.035
MutPred		0.25		Loss of catalytic residue at V349 (P = 0.0386);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100815425;