NM_001136152.1:c.203C>T

Variant names:

• chr3-130092172-C-T
• rs183887858
• NM_001136152.1:c.203C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001136152.1(ALG1L2):​c.203C>T​(p.Thr68Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,612,922 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (1 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.315
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050107837).

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.203C>T	p.Thr68Met	missense	Exon 3 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.158-305G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.203C>T	p.Thr68Met	missense	Exon 3 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.203C>T	p.Thr68Met	missense	Exon 3 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.203C>T	p.Thr68Met	missense	Exon 3 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000613 AC: 152 AN: 248050 AF XY: 0.000601

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.00820

Gnomad EAS exome AF: 0.00104

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.000325 AC: 475 AN: 1460600 Hom.: 1 Cov.: 30 AF XY: 0.000343 AC XY: 249 AN XY: 726610

African (AFR) AF: 0.000120 AC: 4 AN: 33434

American (AMR) AF: 0.000291 AC: 13 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00812 AC: 212 AN: 26120

East Asian (EAS) AF: 0.00111 AC: 44 AN: 39672

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86158

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53288

Middle Eastern (MID) AF: 0.000936 AC: 5 AN: 5340

European-Non Finnish (NFE) AF: 0.000118 AC: 131 AN: 1111642

Other (OTH) AF: 0.000746 AC: 45 AN: 60296

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38 AN XY: 74478

African (AFR) AF: 0.000265 AC: 11 AN: 41568

American (AMR) AF: 0.000196 AC: 3 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000975 Hom.: 0

Bravo AF: 0.000510

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000629 AC: 2

ExAC AF: 0.000503 AC: 61

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.0
DANN	Benign	0.81
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0050	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.32
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.31	T
Polyphen		0.27	B
Vest4		0.16
MVP		0.014
GERP RS		-2.4
Varity_R		0.020
gMVP		0.55
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs183887858; hg19: chr3-129811015; COSMIC: COSV70649254; COSMIC: COSV70649254;