dbSNP rs3213945: AGPS:c.1856-16G>T (chr2-177538058-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003659.4(AGPS):c.1856-16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,246 control chromosomes in the GnomAD database, including 10,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 920 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9862 hom. )

Consequence

AGPS
NM_003659.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0780

Publications

16 publications found

Variant links:

Genes affected

AGPS (HGNC:327): (alkylglycerone phosphate synthase) This gene is a member of the FAD-binding oxidoreductase/transferase type 4 family. It encodes a protein that catalyzes the second step of ether lipid biosynthesis in which acyl-dihydroxyacetonephosphate (DHAP) is converted to alkyl-DHAP by the addition of a long chain alcohol and the removal of a long-chain acid anion. The protein is localized to the inner aspect of the peroxisomal membrane and requires FAD as a cofactor. Mutations in this gene have been associated with rhizomelic chondrodysplasia punctata, type 3 and Zellweger syndrome. [provided by RefSeq, Jul 2008]

AGPS Gene-Disease associations (from GenCC):

alkylglycerone-phosphate synthase deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
rhizomelic chondrodysplasia punctata type 3
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics

AGPS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-177538058-G-T is Benign according to our data. Variant chr2-177538058-G-T is described in ClinVar as Benign. ClinVar VariationId is 259117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003659.4. 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
	AGPS	NM_003659.4	MANE Select	c.1856-16G>T		intron	N/A	NP_003650.1	O00116

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGPS	ENST00000264167.11	TSL:1 MANE Select	c.1856-16G>T	intron	N/A	ENSP00000264167.4	O00116
AGPS	ENST00000642466.2		c.1856-13305G>T	intron	N/A	ENSP00000494433.2	A0A2R8YEL0
AGPS	ENST00000927419.1		c.1853-16G>T	intron	N/A	ENSP00000597478.1

Frequencies

GnomAD3 genomes

AF:

0.0916

AC:

13926

AN:

151972

Hom.:

917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0565

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0724

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.0671

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0931

Gnomad OTH

AF:

0.0976

GnomAD2 exomes

AF:

0.114

AC:

28563

AN:

251092

AF XY:

0.117

show subpopulations

Gnomad AFR exome

AF:

0.0528

Gnomad AMR exome

AF:

0.0664

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.0768

Gnomad NFE exome

AF:

0.0922

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.103

AC:

149805

AN:

1460156

Hom.:

9862

Cov.:

AF XY:

0.104

AC XY:

75859

AN XY:

726430

show subpopulations

African (AFR)

AF:

0.0591

AC:

1973

AN:

33402

American (AMR)

AF:

0.0690

AC:

3081

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3363

AN:

26070

East Asian (EAS)

AF:

0.373

AC:

14786

AN:

39658

South Asian (SAS)

AF:

0.158

AC:

13617

AN:

86206

European-Finnish (FIN)

AF:

0.0795

AC:

4245

AN:

53400

Middle Eastern (MID)

AF:

0.143

AC:

821

AN:

5758

European-Non Finnish (NFE)

AF:

0.0909

AC:

100971

AN:

1110722

Other (OTH)

AF:

0.115

AC:

6948

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

6691

13381

20072

26762

33453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3818

7636

11454

15272

19090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0915

AC:

13921

AN:

152090

Hom.:

920

Cov.:

AF XY:

0.0930

AC XY:

6915

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0564

AC:

2342

AN:

41528

American (AMR)

AF:

0.0725

AC:

1106

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

426

AN:

3470

East Asian (EAS)

AF:

0.357

AC:

1839

AN:

5158

South Asian (SAS)

AF:

0.161

AC:

776

AN:

4818

European-Finnish (FIN)

AF:

0.0671

AC:

711

AN:

10602

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0931

AC:

6327

AN:

67934

Other (OTH)

AF:

0.0975

AC:

206

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

643

1286

1930

2573

3216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0920

Hom.:

1192

Bravo

AF:

0.0909

Asia WGS

AF:

0.231

AC:

800

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Rhizomelic chondrodysplasia punctata type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.5

(source)

DANN

Benign

0.74

PhyloP100

0.078

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over