Genetic Variant ALG1L2:p.Thr4Thr (chr3-130082028-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001136152.1(ALG1L2):c.12T>C(p.Thr4Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0007 in 1,509,910 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 43)

Exomes 𝑓: 0.00074 ( 7 hom. )

Consequence

ALG1L2
NM_001136152.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.149

Publications

0 publications found

Variant links:

Genes affected

ALG1L2 (HGNC:37258): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase like 2) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ALG1L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-130082028-T-C is Benign according to our data. Variant chr3-130082028-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2654130.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.149 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136152.1. 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
	ALG1L2	NM_001136152.1	MANE Select	c.12T>C	p.Thr4Thr	synonymous	Exon 1 of 8	NP_001129624.1	C9J202

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.12T>C	p.Thr4Thr	synonymous	Exon 1 of 8	ENSP00000479850.1	C9J202
ALG1L2	ENST00000698236.2		c.12T>C	p.Thr4Thr	synonymous	Exon 1 of 9	ENSP00000513618.2	A0A8V8TNA5
ALG1L2	ENST00000698237.1		c.12T>C	p.Thr4Thr	synonymous	Exon 1 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes

AF:

0.000337

AC:

AN:

151142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000697

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000236

AC:

AN:

148248

AF XY:

0.000292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000429

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000579

Gnomad OTH exome

AF:

0.000244

GnomAD4 exome

AF:

0.000740

AC:

1006

AN:

1358768

Hom.:

Cov.:

AF XY:

0.000706

AC XY:

474

AN XY:

671442

show subpopulations

African (AFR)

AF:

0.0000319

AC:

AN:

31350

American (AMR)

AF:

0.0000287

AC:

AN:

34804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24796

East Asian (EAS)

AF:

0.00

AC:

AN:

35614

South Asian (SAS)

AF:

0.00

AC:

AN:

78024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3956

European-Non Finnish (NFE)

AF:

0.000915

AC:

956

AN:

1044696

Other (OTH)

AF:

0.000848

AC:

AN:

56610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.000337

AC:

AN:

151142

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

AN XY:

73804

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000965

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.000697

AC:

AN:

67444

Other (OTH)

AF:

0.00

AC:

AN:

2074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000000111022), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000753

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

(source)

DANN

Benign

0.84

PhyloP100

0.15

PromoterAI

0.025

Neutral

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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