2-73641201-A-G

Position:

• chr2-73641201-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003960.4(NAT8):​c.428T>C​(p.Phe143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,728 control chromosomes in the GnomAD database, including 46,882 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (8694 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38188 hom.)
• Consequence: NAT8 NM_003960.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

Genes affected

NAT8 (HGNC:18069): (N-acetyltransferase 8 (putative)) This gene, isolated using the differential display method to detect tissue-specific genes, is specifically expressed in kidney and liver. The encoded protein shows amino acid sequence similarity to N-acetyltransferases. A similar protein in Xenopus affects cell adhesion and gastrulation movements, and may be localized in the secretory pathway. A highly similar paralog is found in a cluster with this gene. [provided by RefSeq, Sep 2008]

ALMS1P1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3671985E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT8	NM_003960.4	c.428T>C	p.Phe143Ser	missense_variant	2/2	ENST00000272425.4	NP_003951.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT8	ENST00000272425.4	c.428T>C	p.Phe143Ser	missense_variant	2/2	1	NM_003960.4	ENSP00000272425.3
ALMS1P1	ENST00000652439.1	n.119A>G		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45577 AN: 151758 Hom.: 8663 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.283

GnomAD3 exomes AF: 0.213 AC: 53561 AN: 251390 Hom.: 7371 AF XY: 0.205 AC XY: 27826 AN XY: 135882

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.00402

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.218 AC: 318052 AN: 1461852 Hom.: 38188 Cov.: 33 AF XY: 0.215 AC XY: 156248 AN XY: 727228

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.00413

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.301 AC: 45663 AN: 151876 Hom.: 8694 Cov.: 32 AF XY: 0.293 AC XY: 21760 AN XY: 74258

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.00445

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.279

Alfa AF: 0.256 Hom.: 2813

Bravo AF: 0.317

TwinsUK AF: 0.219 AC: 813

ALSPAC AF: 0.218 AC: 839

ESP6500AA AF: 0.527 AC: 2321

ESP6500EA AF: 0.223 AC: 1917

ExAC AF: 0.219 AC: 26536

Asia WGS AF: 0.102 AC: 356 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.13
DANN	Benign	0.28
DEOGEN2	Benign	0.077	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.073	T
MetaRNN	Benign	0.00024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.19	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	3.6	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.0040
ClinPred		0.00037	T
GERP RS		-7.7
Varity_R		0.042
gMVP		0.50

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: rs13538; hg19: chr2-73868328; COSMIC: COSV55542239; COSMIC: COSV55542239;