2-73641545-A-T

Variant names:

• chr2-73641545-A-T
• rs78164441
• NM_003960.4:c.84T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003960.4(NAT8):​c.84T>A​(p.His28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,610,478 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (109 hom.)
• Consequence: NAT8 NM_003960.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.217
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020417273).
• BP6: Variant 2-73641545-A-T is Benign according to our data. Variant chr2-73641545-A-T is described in ClinVar as Benign. ClinVar VariationId is 790819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003960.4. 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
	NAT8	NM_003960.4	MANE Select	c.84T>A	p.His28Gln	missense	Exon 2 of 2	NP_003951.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT8	ENST00000272425.4	TSL:1 MANE Select	c.84T>A	p.His28Gln	missense	Exon 2 of 2	ENSP00000272425.3	Q9UHE5
	NAT8	ENST00000852385.1		c.84T>A	p.His28Gln	missense	Exon 2 of 2	ENSP00000522444.1
	NAT8	ENST00000852386.1		c.84T>A	p.His28Gln	missense	Exon 2 of 2	ENSP00000522445.1

Frequencies

GnomAD3 genomes AF: 0.00267 AC: 406 AN: 152116 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00633 AC: 1565 AN: 247094 AF XY: 0.00584

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0811

Gnomad FIN exome AF: 0.000423

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00417

GnomAD4 exome AF: 0.00207 AC: 3020 AN: 1458244 Hom.: 109 Cov.: 31 AF XY: 0.00202 AC XY: 1464 AN XY: 725202

African (AFR) AF: 0.0000897 AC: 3 AN: 33446

American (AMR) AF: 0.000158 AC: 7 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25826

East Asian (EAS) AF: 0.0648 AC: 2571 AN: 39678

South Asian (SAS) AF: 0.00139 AC: 119 AN: 85528

European-Finnish (FIN) AF: 0.000714 AC: 38 AN: 53222

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5752

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110260

Other (OTH) AF: 0.00433 AC: 261 AN: 60224

GnomAD4 genome AF: 0.00268 AC: 408 AN: 152234 Hom.: 17 Cov.: 32 AF XY: 0.00320 AC XY: 238 AN XY: 74436

African (AFR) AF: 0.000120 AC: 5 AN: 41572

American (AMR) AF: 0.000459 AC: 7 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0729 AC: 377 AN: 5168

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4820

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.000293 Hom.: 0

Bravo AF: 0.00326

ExAC AF: 0.00600 AC: 729

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.5
DANN	Benign	0.78
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.22
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.12
Sift	Benign	0.083	T
Sift4G	Benign	0.18	T
Polyphen		0.43	B
Vest4		0.24
MutPred		0.51		Loss of methylation at R23 (P = 0.1122)
MVP		0.44
MPC		0.0076
ClinPred		0.055	T
GERP RS		-0.82
Varity_R		0.13
gMVP		0.85
Mutation Taster		=96/4	polymorphism (auto)

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: rs78164441; hg19: chr2-73868672; COSMIC: COSV99721920; COSMIC: COSV99721920;