1-15573706-G-C

Variant names:

• chr1-15573706-G-C
• rs202068651
• NM_024758.5:c.1004C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024758.5(AGMAT):​c.1004C>G​(p.Ala335Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A335V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: AGMAT NM_024758.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32610464).

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.1004C>G	p.Ala335Gly	missense	Exon 7 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.1004C>G	p.Ala335Gly	missense	Exon 7 of 7	ENSP00000364986.3	Q9BSE5
	DNAJC16	ENST00000375849.5	TSL:1	c.1950-1054G>C		intron	N/A	ENSP00000365009.1	Q5TDH4
	DNAJC16	ENST00000483270.1	TSL:1	n.2199-1054G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461808 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.74
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.065	N
PhyloP100		2.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.2	N
REVEL	Uncertain	0.36
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.015	B
Vest4		0.30
MutPred		0.80		Loss of stability (P = 0.0998)
MVP		0.82
MPC		0.40
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.81
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs202068651; hg19: chr1-15900201;