3-130092142-C-A

Variant names:

• chr3-130092142-C-A
• rs142052214
• NM_001136152.1:c.173C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136152.1(ALG1L2):​c.173C>A​(p.Thr58Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,274 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. T58M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (1 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34137386).

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.173C>A	p.Thr58Lys	missense	Exon 3 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.158-275G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.173C>A	p.Thr58Lys	missense	Exon 3 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.173C>A	p.Thr58Lys	missense	Exon 3 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.173C>A	p.Thr58Lys	missense	Exon 3 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 249190 AF XY: 0.0000222

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461274 Hom.: 1 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726934

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

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

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

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111792

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6480

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.61
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.34	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.7
PrimateAI	Uncertain	0.61	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.83	P
Vest4		0.34
MVP		0.067
GERP RS		0.26
Varity_R		0.031
gMVP		0.79
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142052214; hg19: chr3-129810985;