chr3-130094411-C-T

Variant names:

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

Variant summary

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

The NM_001136152.1(ALG1L2):​c.322C>T​(p.Pro108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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>T	p.Pro108Ser	missense	Exon 5 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.-107G>A		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>T	p.Pro108Ser	missense	Exon 5 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.361C>T	p.Pro121Ser	missense	Exon 6 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.322C>T	p.Pro108Ser	missense	Exon 5 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443444 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718526

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

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111100

Other (OTH) AF: 0.00 AC: 0 AN: 60096

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Uncertain	0.60	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		4.8
PrimateAI	Uncertain	0.51	T
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.41
MVP		0.30
GERP RS		1.2
Varity_R		0.084
gMVP		0.73
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;