chr17-45090495-G-C

Variant names:

• chr17-45090495-G-C
• rs10491142
• NM_021079.5:c.386-3190G>C

Variant summary

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

The NM_021079.5(NMT1):​c.386-3190G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,146 control chromosomes in the GnomAD database, including 1,006 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 0.11 (1006 hom., cov: 31)
• Consequence: NMT1 NM_021079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 3 publications found

Genes affected

NMT1 (HGNC:7857): (N-myristoyltransferase 1) Myristate, a rare 14-carbon saturated fatty acid, is cotranslationally attached by an amide linkage to the N-terminal glycine residue of cellular and viral proteins with diverse functions. N-myristoyltransferase (NMT; EC 2.3.1.97) catalyzes the transfer of myristate from CoA to proteins. N-myristoylation appears to be irreversible and is required for full expression of the biologic activities of several N-myristoylated proteins, including the alpha subunit of the signal-transducing guanine nucleotide-binding protein (G protein) GO (GNAO1; MIM 139311) (Duronio et al., 1992 [PubMed 1570339]).[supplied by OMIM, Nov 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021079.5. 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
	NMT1	NM_021079.5	MANE Select	c.386-3190G>C		intron	N/A	NP_066565.1	P30419-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMT1	ENST00000258960.7	TSL:1 MANE Select	c.386-3190G>C		intron	N/A	ENSP00000258960.2	P30419-1
	NMT1	ENST00000587014.2	TSL:1	n.412-3190G>C		intron	N/A
	NMT1	ENST00000592782.5	TSL:5	c.386-3190G>C		intron	N/A	ENSP00000468424.1	P30419-1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16570 AN: 152026 Hom.: 1005 Cov.: 31

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.109 AC: 16570 AN: 152146 Hom.: 1006 Cov.: 31 AF XY: 0.109 AC XY: 8118 AN XY: 74388

African (AFR) AF: 0.0389 AC: 1615 AN: 41544

American (AMR) AF: 0.137 AC: 2086 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3464

East Asian (EAS) AF: 0.118 AC: 607 AN: 5164

South Asian (SAS) AF: 0.0794 AC: 382 AN: 4814

European-Finnish (FIN) AF: 0.152 AC: 1611 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9306 AN: 67986

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.0685 Hom.: 88

Bravo AF: 0.106

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.15
Mutation Taster		=100/0	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: rs10491142; hg19: chr17-43167863;