3-130094411-C-G

Variant names:

• chr3-130094411-C-G
• rs779133862
• NM_001136152.1:c.322C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136152.1(ALG1L2):​c.322C>G​(p.Pro108Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P108T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• Publications: 0 publications found

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]

LINC02014 (HGNC:52849): (long intergenic non-protein coding RNA 2014)

ENSG00000291081 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.322C>G	p.Pro108Ala	missense	Exon 5 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.-107G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.322C>G	p.Pro108Ala	missense	Exon 5 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.361C>G	p.Pro121Ala	missense	Exon 6 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.322C>G	p.Pro108Ala	missense	Exon 5 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000430 AC: 1 AN: 232484 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Uncertain	0.47	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.8
PrimateAI	Uncertain	0.51	T
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.29
MVP		0.30
GERP RS		1.2
Varity_R		0.070
gMVP		0.66
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs779133862; hg19: chr3-129813254;