Variant 16-5071856-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019109.5(ALG1):c.7G>A(p.Ala3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALG1
NM_019109.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

ALG1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15562272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ALG1	NM_019109.5 linkuse as main transcript	c.7G>A	p.Ala3Thr	missense_variant	1/13	ENST00000262374.10	NP_061982.3
ALG1	XM_017023457.3 linkuse as main transcript	c.7G>A	p.Ala3Thr	missense_variant	1/12		XP_016878946.1
ALG1	XR_007064892.1 linkuse as main transcript	n.14G>A		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG1	ENST00000262374.10 linkuse as main transcript	c.7G>A	p.Ala3Thr	missense_variant	1/13	1	NM_019109.5	ENSP00000262374	P1	Q9BT22-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722638

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:

0.00

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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.7G>A (p.A3T) alteration is located in exon 1 (coding exon 1) of the ALG1 gene. This alteration results from a G to A substitution at nucleotide position 7, causing the alanine (A) at amino acid position 3 to be replaced by a threonine (T). 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

Benign

0.11

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.43

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.57

N;.

REVEL

Benign

0.16

Sift

Benign

0.26

T;.

Sift4G

Benign

0.11

T;D

Polyphen

0.51

P;.

Vest4

0.28

MutPred

0.27

Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.81

MPC

0.059

ClinPred

0.80

GERP RS

2.7

Varity_R

0.046

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over