rs544301585

Variant names:

• chr3-130092201-G-A
• rs544301585
• NM_001136152.1:c.232G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-130092201-G-A
• chr3-130092201-G-C
• chr3-130092201-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001136152.1(ALG1L2):​c.232G>A​(p.Val78Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,611,578 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0670
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018144906).

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.232G>A	p.Val78Ile	missense	Exon 3 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.158-334C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.232G>A	p.Val78Ile	missense	Exon 3 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.232G>A	p.Val78Ile	missense	Exon 3 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.232G>A	p.Val78Ile	missense	Exon 3 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000895 AC: 22 AN: 245930 AF XY: 0.0000673

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000459 AC: 67 AN: 1459222 Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27 AN XY: 725908

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.0000224 AC: 1 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00101 AC: 40 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4876

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111358

Other (OTH) AF: 0.000415 AC: 25 AN: 60222

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6 AN XY: 74498

African (AFR) AF: 0.0000481 AC: 2 AN: 41590

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.00115 AC: 4 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	0.098
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.6
DANN	Benign	0.84
DEOGEN2	Benign	0.052	T
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.018	T
MutationAssessor	Benign	0.71	N
PhyloP100		0.067
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.42	T
Polyphen		0.025	B
Vest4		0.10
MVP		0.030
GERP RS		-0.88
Varity_R		0.022
gMVP		0.41
Mutation Taster		=98/2	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: rs544301585; hg19: chr3-129811044;