chr3-130093136-C-T

Position:

• chr3-130093136-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136152.1(ALG1L2):​c.289C>T​(p.Pro97Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.22

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG1L2	NM_001136152.1	c.289C>T	p.Pro97Ser	missense_variant	4/8	ENST00000425059.1	NP_001129624.1
LINC02014	NR_146710.1	n.157+1012G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG1L2	ENST00000425059.1	c.289C>T	p.Pro97Ser	missense_variant	4/8	5	NM_001136152.1	ENSP00000479850.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250878 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135666

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2021

The c.289C>T (p.P97S) alteration is located in exon 4 (coding exon 4) of the ALG1L2 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the proline (P) at amino acid position 97 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Benign	0.71
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Uncertain	0.68	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.57	T
Sift4G	Uncertain	0.015	D
Polyphen		0.72	P
Vest4		0.60
MVP		0.11
GERP RS		1.2
Varity_R		0.084
gMVP		0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs756601914; hg19: chr3-129811979;