chr3-130091350-C-T

Variant names:

• chr3-130091350-C-T
• rs568221197
• NM_001136152.1:c.110C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136152.1(ALG1L2):​c.110C>T​(p.Thr37Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000751 in 1,597,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.225
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056136727).

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.110C>T	p.Thr37Met	missense	Exon 2 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.249-230G>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.110C>T	p.Thr37Met	missense	Exon 2 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.110C>T	p.Thr37Met	missense	Exon 2 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.110C>T	p.Thr37Met	missense	Exon 2 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000845 AC: 20 AN: 236632 AF XY: 0.0000696

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.000254

Gnomad NFE exome AF: 0.0000724

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000768 AC: 111 AN: 1445006 Hom.: 0 Cov.: 34 AF XY: 0.0000737 AC XY: 53 AN XY: 719264

African (AFR) AF: 0.0000299 AC: 1 AN: 33402

American (AMR) AF: 0.0000671 AC: 3 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86152

European-Finnish (FIN) AF: 0.000308 AC: 12 AN: 38942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1111730

Other (OTH) AF: 0.0000665 AC: 4 AN: 60120

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

African (AFR) AF: 0.0000724 AC: 3 AN: 41452

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000992 AC: 12

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	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	2.6
DANN	Benign	0.72
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.056	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.23
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.10	T
Polyphen		0.0090	B
Vest4		0.13
MVP		0.014
GERP RS		-0.83
Varity_R		0.024
gMVP		0.46
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: rs568221197; hg19: chr3-129810193; COSMIC: COSV101405968; COSMIC: COSV101405968;