3-130091293-T-C

Variant names:

• chr3-130091293-T-C
• NM_001136152.1:c.53T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136152.1(ALG1L2):​c.53T>C​(p.Phe18Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25055075).

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.53T>C	p.Phe18Ser	missense	Exon 2 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.249-173A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.53T>C	p.Phe18Ser	missense	Exon 2 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.53T>C	p.Phe18Ser	missense	Exon 2 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.53T>C	p.Phe18Ser	missense	Exon 2 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447078 Hom.: 0 Cov.: 39 AF XY: 0.00000139 AC XY: 1 AN XY: 720302

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40968

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111748

Other (OTH) AF: 0.00 AC: 0 AN: 60130

GnomAD4 genome Cov.: 33

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	0.17
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.085	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.25	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.5
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.27	T
Polyphen		0.67	P
Vest4		0.28
MVP		0.24
GERP RS		1.2
Varity_R		0.17
gMVP		0.59
Mutation Taster		=79/21	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

hg19: chr3-129810136;