7-101172440-C-A

Variant names:

• chr7-101172440-C-A
• rs551457672
• NM_198571.3:c.749G>T

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.749G>T​(p.Arg250Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,268 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. 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. R250P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NAT16 NM_198571.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• 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=0.0571191).

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.749G>T	p.Arg250Leu	missense	Exon 4 of 4	NP_940973.2	Q8N8M0-1
	NAT16	NM_001369694.1		c.749G>T	p.Arg250Leu	missense	Exon 5 of 5	NP_001356623.1	Q8N8M0-1
	NAT16	NM_001369695.1		c.749G>T	p.Arg250Leu	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.749G>T	p.Arg250Leu	missense	Exon 4 of 4	ENSP00000300303.2	Q8N8M0-1
	NAT16	ENST00000455377.5	TSL:1	c.749G>T	p.Arg250Leu	missense	Exon 5 of 5	ENSP00000395125.1	Q8N8M0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445268 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 718680

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33124

American (AMR) AF: 0.00 AC: 0 AN: 43302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39116

South Asian (SAS) AF: 0.00 AC: 0 AN: 84748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107326

Other (OTH) AF: 0.00 AC: 0 AN: 59802

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.38
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.045
Sift	Benign	0.087	T
Sift4G	Uncertain	0.031	D
Polyphen		0.016	B
Vest4		0.25
MutPred		0.33		Loss of disorder (P = 0.0697)
MVP		0.099
MPC		0.82
ClinPred		0.20	T
GERP RS		-4.8
Varity_R		0.073
gMVP		0.43
Mutation Taster		=94/6	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: rs551457672; hg19: chr7-100815721;