chr2-73640770-A-G

Variant names:

• chr2-73640770-A-G
• rs1879662
• NM_003960.4:c.*175T>C

Variant summary

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

The NM_003960.4(NAT8):​c.*175T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 629,454 control chromosomes in the GnomAD database, including 231,816 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 (57239 hom., cov: 33)
  • Exomes 𝑓: 0.85 (174577 hom.)
• Consequence: NAT8 NM_003960.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT8	NM_003960.4	c.*175T>C		3_prime_UTR_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.*175T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_003960.4	ENSP00000272425.3
ALMS1P1	ENST00000755941.1	n.48A>G		non_coding_transcript_exon_variant	Exon 1 of 6
ALMS1P1	ENST00000755937.1	n.-62A>G		upstream_gene_variant
ALMS1P1	ENST00000755942.1	n.-3A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131711 AN: 152110 Hom.: 57191 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.869

GnomAD4 exome AF: 0.853 AC: 407202 AN: 477226 Hom.: 174577 AF XY: 0.853 AC XY: 206498 AN XY: 242102

African (AFR) AF: 0.865 AC: 11743 AN: 13572

American (AMR) AF: 0.935 AC: 14983 AN: 16018

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 10619 AN: 12886

East Asian (EAS) AF: 0.670 AC: 20479 AN: 30548

South Asian (SAS) AF: 0.830 AC: 21756 AN: 26198

European-Finnish (FIN) AF: 0.849 AC: 24843 AN: 29262

Middle Eastern (MID) AF: 0.847 AC: 1684 AN: 1988

European-Non Finnish (NFE) AF: 0.869 AC: 278499 AN: 320498

Other (OTH) AF: 0.861 AC: 22596 AN: 26256

GnomAD4 genome AF: 0.866 AC: 131818 AN: 152228 Hom.: 57239 Cov.: 33 AF XY: 0.865 AC XY: 64387 AN XY: 74436

African (AFR) AF: 0.875 AC: 36373 AN: 41560

American (AMR) AF: 0.917 AC: 13985 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2834 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3511 AN: 5170

South Asian (SAS) AF: 0.824 AC: 3975 AN: 4826

European-Finnish (FIN) AF: 0.851 AC: 9033 AN: 10610

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

European-Non Finnish (NFE) AF: 0.870 AC: 59152 AN: 68022

Other (OTH) AF: 0.866 AC: 1829 AN: 2112

Alfa AF: 0.872 Hom.: 7193

Bravo AF: 0.870

Asia WGS AF: 0.776 AC: 2698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.69
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1879662; hg19: chr2-73867897;