rs568221197

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-130091350-C-A
• chr3-130091350-C-G
• chr3-130091350-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136152.1(ALG1L2):​c.110C>A​(p.Thr37Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,445,010 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T37M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ALG1L2 NM_001136152.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08101457).

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>A	p.Thr37Lys	missense	Exon 2 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.249-230G>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.110C>A	p.Thr37Lys	missense	Exon 2 of 8	ENSP00000479850.1	C9J202
	ALG1L2	ENST00000698236.2		c.110C>A	p.Thr37Lys	missense	Exon 2 of 9	ENSP00000513618.2	A0A8V8TNA5
	ALG1L2	ENST00000698237.1		c.110C>A	p.Thr37Lys	missense	Exon 2 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1445010 Hom.: 0 Cov.: 34 AF XY: 0.00000417 AC XY: 3 AN XY: 719266

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38942

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111734

Other (OTH) AF: 0.00 AC: 0 AN: 60120

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.23
DANN	Benign	0.74
DEOGEN2	Benign	0.0078	T
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.081	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.23
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.88	T
Polyphen		0.056	B
Vest4		0.18
MVP		0.014
GERP RS		-0.83
Varity_R		0.034
gMVP		0.52
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;