2-73641993-G-A

Variant names:

• chr2-73641993-G-A
• rs6744273
• NM_003960.4:c.-74-291C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003960.4(NAT8):​c.-74-291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,016 control chromosomes in the GnomAD database, including 57,152 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57152 hom., cov: 31)
• Consequence: NAT8 NM_003960.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT8	NM_003960.4	c.-74-291C>T		intron_variant	Intron 1 of 1	ENST00000272425.4	NP_003951.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT8	ENST00000272425.4	c.-74-291C>T		intron_variant	Intron 1 of 1	1	NM_003960.4	ENSP00000272425.3

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131527 AN: 151898 Hom.: 57104 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.869

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.866 AC: 131634 AN: 152016 Hom.: 57152 Cov.: 31 AF XY: 0.865 AC XY: 64266 AN XY: 74308

African (AFR) AF: 0.875 AC: 36290 AN: 41454

American (AMR) AF: 0.917 AC: 13964 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2832 AN: 3468

East Asian (EAS) AF: 0.680 AC: 3496 AN: 5144

South Asian (SAS) AF: 0.822 AC: 3955 AN: 4814

European-Finnish (FIN) AF: 0.851 AC: 9024 AN: 10602

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59113 AN: 67988

Other (OTH) AF: 0.866 AC: 1832 AN: 2116

Alfa AF: 0.871 Hom.: 6744

Bravo AF: 0.870

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.31
PhyloP100		-0.72
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs6744273; hg19: chr2-73869120;