3-130091293-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG1L2	NM_001136152.1	c.53T>C	p.Phe18Ser	missense_variant	Exon 2 of 8	ENST00000425059.1	NP_001129624.1
LINC02014	NR_146710.1	n.249-173A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG1L2	ENST00000425059.1	c.53T>C	p.Phe18Ser	missense_variant	Exon 2 of 8	5	NM_001136152.1	ENSP00000479850.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53T>C (p.F18S) alteration is located in exon 2 (coding exon 2) of the ALG1L2 gene. This alteration results from a T to C substitution at nucleotide position 53, causing the phenylalanine (F) at amino acid position 18 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	0.17
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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-129810136;