Variant 19-58350555-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000263100.8(A1BG):c.1007T>G(p.Leu336Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

A1BG
ENST00000263100.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.374

Variant links:

Genes affected

A1BG (HGNC:5): (alpha-1-B glycoprotein) The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins. [provided by RefSeq, Jul 2008]

A1BG links:

A1BG-AS1 (HGNC:37133): (A1BG antisense RNA 1)

A1BG-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1BG	NM_130786.4 linkuse as main transcript	c.1007T>G	p.Leu336Arg	missense_variant	6/8	ENST00000263100.8	NP_570602.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1BG	ENST00000263100.8 linkuse as main transcript	c.1007T>G	p.Leu336Arg	missense_variant	6/8	1	NM_130786.4	ENSP00000263100	P1	P04217-1
A1BG-AS1	ENST00000670460.1 linkuse as main transcript	n.127+2711A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000721

AC:

AN:

138702

Hom.:

AF XY:

0.0000133

AC XY:

AN XY:

75008

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000207

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394174

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.29e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.1007T>G (p.L336R) alteration is located in exon 6 (coding exon 6) of the A1BG gene. This alteration results from a T to G substitution at nucleotide position 1007, causing the leucine (L) at amino acid position 336 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.52

M_CAP

Benign

0.060

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.6

MutationTaster

Benign

0.69

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.18

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.77

MutPred

0.74

Loss of stability (P = 0.0113);

MVP

0.61

MPC

1.3

ClinPred

0.87

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.81

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over