1-15583355-C-G

Variant names:

• chr1-15583355-C-G
• rs6429757
• NM_024758.5:c.313G>C

Variant summary

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

The NM_024758.5(AGMAT):​c.313G>C​(p.Gly105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,613,286 control chromosomes in the GnomAD database, including 266,065 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33358 hom., cov: 32)
  • Exomes 𝑓: 0.56 (232707 hom.)
• Consequence: AGMAT NM_024758.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 33 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.654469E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

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.313G>C	p.Gly105Arg	missense	Exon 2 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.313G>C	p.Gly105Arg	missense	Exon 2 of 7	ENSP00000364986.3	Q9BSE5
	DNAJC16	ENST00000483270.1	TSL:1	n.2726+7883C>G		intron	N/A
	AGMAT	ENST00000909207.1		c.313G>C	p.Gly105Arg	missense	Exon 2 of 7	ENSP00000579266.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98213 AN: 152030 Hom.: 33306 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.598

GnomAD2 exomes AF: 0.558 AC: 140007 AN: 250720 AF XY: 0.550

Gnomad AFR exome AF: 0.860

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.509

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.560 AC: 817540 AN: 1461138 Hom.: 232707 Cov.: 58 AF XY: 0.556 AC XY: 403884 AN XY: 726902

African (AFR) AF: 0.864 AC: 28914 AN: 33476

American (AMR) AF: 0.434 AC: 19382 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 13495 AN: 26122

East Asian (EAS) AF: 0.622 AC: 24693 AN: 39696

South Asian (SAS) AF: 0.440 AC: 37922 AN: 86212

European-Finnish (FIN) AF: 0.662 AC: 35344 AN: 53374

Middle Eastern (MID) AF: 0.556 AC: 3189 AN: 5740

European-Non Finnish (NFE) AF: 0.558 AC: 620152 AN: 1111470

Other (OTH) AF: 0.571 AC: 34449 AN: 60364

GnomAD4 genome AF: 0.646 AC: 98314 AN: 152148 Hom.: 33358 Cov.: 32 AF XY: 0.645 AC XY: 47996 AN XY: 74356

African (AFR) AF: 0.858 AC: 35651 AN: 41530

American (AMR) AF: 0.530 AC: 8087 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3227 AN: 5180

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4818

European-Finnish (FIN) AF: 0.673 AC: 7118 AN: 10576

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38337 AN: 67988

Other (OTH) AF: 0.594 AC: 1256 AN: 2114

Alfa AF: 0.578 Hom.: 8369

Bravo AF: 0.645

TwinsUK AF: 0.552 AC: 2048

ALSPAC AF: 0.558 AC: 2151

ESP6500AA AF: 0.851 AC: 3749

ESP6500EA AF: 0.553 AC: 4755

ExAC AF: 0.566 AC: 68685

Asia WGS AF: 0.561 AC: 1952 AN: 3478

EpiCase AF: 0.547

EpiControl AF: 0.542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.8
DANN	Benign	0.64
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	6.7e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.99	N
PhyloP100		0.61
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	5.3	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.41		Gain of MoRF binding (P = 0.0106)
MPC		0.36
ClinPred		0.0018	T
GERP RS		-1.4
Varity_R		0.15
gMVP		0.74
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: rs6429757; hg19: chr1-15909850; COSMIC: COSV65435864; COSMIC: COSV65435864;