chr1-15583249-C-T

Position:

• chr1-15583249-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024758.5(AGMAT):​c.419G>A​(p.Arg140Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,544 control chromosomes in the GnomAD database, including 56,087 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.32 (9264 hom., cov: 31)
  • Exomes 𝑓: 0.25 (46823 hom.)
• Consequence: AGMAT NM_024758.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.970299E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGMAT	NM_024758.5	c.419G>A	p.Arg140Gln	missense_variant	2/7	ENST00000375826.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGMAT	ENST00000375826.4	c.419G>A	p.Arg140Gln	missense_variant	2/7	1	NM_024758.5	P1
DNAJC16	ENST00000483270.1	n.2726+7777C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48690 AN: 151784 Hom.: 9237 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.303

GnomAD3 exomes AF: 0.242 AC: 60937 AN: 251288 Hom.: 8600 AF XY: 0.241 AC XY: 32728 AN XY: 135828

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.0657

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.246 AC: 359591 AN: 1461642 Hom.: 46823 Cov.: 44 AF XY: 0.245 AC XY: 178308 AN XY: 727130

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.0775

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.321 AC: 48755 AN: 151902 Hom.: 9264 Cov.: 31 AF XY: 0.318 AC XY: 23577 AN XY: 74224

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.300

Alfa AF: 0.259 Hom.: 13532

Bravo AF: 0.323

ESP6500AA AF: 0.525 AC: 2311

ESP6500EA AF: 0.248 AC: 2130

ExAC AF: 0.251 AC: 30439

Asia WGS AF: 0.171 AC: 594 AN: 3478

EpiCase AF: 0.253

EpiControl AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.00060	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.33	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.076
Sift	Benign	0.62	T
Sift4G	Benign	0.62	T
Polyphen		0.016	B
Vest4		0.038
MPC		0.35
ClinPred		0.00083	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.092
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11580170; hg19: chr1-15909744; COSMIC: COSV65435863; COSMIC: COSV65435863;