2-73641201-A-T

Variant names:

• chr2-73641201-A-T
• rs13538
• NM_003960.4:c.428T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003960.4(NAT8):​c.428T>A​(p.Phe143Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAT8 NM_003960.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.135474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT8	NM_003960.4	c.428T>A	p.Phe143Tyr	missense_variant	Exon 2 of 2	ENST00000272425.4	NP_003951.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT8	ENST00000272425.4	c.428T>A	p.Phe143Tyr	missense_variant	Exon 2 of 2	1	NM_003960.4	ENSP00000272425.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.14
DANN	Benign	0.67
DEOGEN2	Benign	0.074	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.073	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.79	N
PhyloP100		-0.087
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.049
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.016	D
Polyphen		0.16	B
Vest4		0.10
MutPred		0.53		Gain of phosphorylation at F143 (P = 0.0939);
MVP		0.055
MPC		0.0048
ClinPred		0.39	T
GERP RS		-7.7
Varity_R		0.23
gMVP		0.47
Mutation Taster		=97/3	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: rs13538; hg19: chr2-73868328;