chr3-130092174-C-T

Variant names:

• chr3-130092174-C-T
• rs73210757
• NM_001136152.1:c.205C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001136152.1(ALG1L2):​c.205C>T​(p.Arg69Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 1,612,912 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (44 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.395
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076847076).
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.205C>T	p.Arg69Cys	missense	Exon 3 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.158-307G>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.205C>T	p.Arg69Cys	missense	Exon 3 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.205C>T	p.Arg69Cys	missense	Exon 3 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.205C>T	p.Arg69Cys	missense	Exon 3 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 703 AN: 152212 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00800

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00470 AC: 1167 AN: 248092 AF XY: 0.00489

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00543

Gnomad NFE exome AF: 0.00816

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00726 AC: 10611 AN: 1460582 Hom.: 44 Cov.: 31 AF XY: 0.00711 AC XY: 5165 AN XY: 726592

African (AFR) AF: 0.00117 AC: 39 AN: 33438

American (AMR) AF: 0.00148 AC: 66 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.000894 AC: 77 AN: 86152

European-Finnish (FIN) AF: 0.00539 AC: 287 AN: 53294

Middle Eastern (MID) AF: 0.00150 AC: 8 AN: 5338

European-Non Finnish (NFE) AF: 0.00877 AC: 9745 AN: 1111614

Other (OTH) AF: 0.00569 AC: 343 AN: 60298

GnomAD4 genome AF: 0.00461 AC: 703 AN: 152330 Hom.: 4 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74494

African (AFR) AF: 0.00123 AC: 51 AN: 41568

American (AMR) AF: 0.00203 AC: 31 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00546 AC: 58 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00800 AC: 544 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00631 Hom.: 2

Bravo AF: 0.00430

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00943 AC: 30

ExAC AF: 0.00525 AC: 637

Asia WGS AF: 0.000577 AC: 3 AN: 3478

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	0.083
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.52
DEOGEN2	Benign	0.054	T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0077	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.40
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.17	T
Polyphen		0.017	B
Vest4		0.13
MVP		0.22
GERP RS		1.2
Varity_R		0.13
gMVP		0.55

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: rs73210757; hg19: chr3-129811017; COSMIC: COSV70649857; COSMIC: COSV70649857;