rs1449683297

Variant names:

• chr1-15577783-C-G
• rs1449683297
• NM_024758.5:c.802G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-15577783-C-G
• chr1-15577783-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024758.5(AGMAT):​c.802G>C​(p.Gly268Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G268D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: AGMAT NM_024758.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

Genes affected

AGMAT (HGNC:18407): (agmatinase (putative)) Predicted to enable agmatinase activity. Predicted to be involved in putrescine biosynthetic process from arginine, using agmatinase. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC16 (HGNC:29157): (DnaJ heat shock protein family (Hsp40) member C16) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11179668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024758.5. 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
	AGMAT	NM_024758.5	MANE Select	c.802G>C	p.Gly268Arg	missense	Exon 5 of 7	NP_079034.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGMAT	ENST00000375826.4	TSL:1 MANE Select	c.802G>C	p.Gly268Arg	missense	Exon 5 of 7	ENSP00000364986.3	Q9BSE5
	DNAJC16	ENST00000483270.1	TSL:1	n.2726+2311C>G		intron	N/A
	AGMAT	ENST00000909207.1		c.802G>C	p.Gly268Arg	missense	Exon 5 of 7	ENSP00000579266.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251470 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461890 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.062
Sift	Benign	0.042	D
Sift4G	Benign	0.071	T
Polyphen		0.022	B
Vest4		0.28
MutPred		0.58		Gain of solvent accessibility (P = 0.0471)
MVP		0.29
MPC		0.37
ClinPred		0.20	T
GERP RS		4.0
Varity_R		0.17
gMVP		0.59
Mutation Taster		=86/14	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: rs1449683297; hg19: chr1-15904278;