rs121908850

Variant names:

• chr12-34026832-G-A
• rs121908850
• NM_032834.4:c.1339G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-34026832-G-A
• chr12-34026832-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_032834.4(ALG10):​c.1339G>A​(p.Val447Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ALG10 NM_032834.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

Genes affected

ALG10 (HGNC:23162): (ALG10 alpha-1,2-glucosyltransferase) This gene encodes a membrane-associated protein that adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. That is, it transfers the terminal glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc2Man9GlcNAc(2)-PP-Dol. The rat protein homolog was shown to specifically modulate the gating function of the rat neuronal ether-a-go-go (EAG) potassium ion channel. [provided by RefSeq, Jan 2010]

ENSG00000245482 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16069347).
• BP6: Variant 12-34026832-G-A is Benign according to our data. Variant chr12-34026832-G-A is described in ClinVar as Benign. ClinVar VariationId is 6496.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032834.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG10	NM_032834.4	MANE Select	c.1339G>A	p.Val447Ile	missense	Exon 3 of 3	NP_116223.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG10	ENST00000266483.7	TSL:1 MANE Select	c.1339G>A	p.Val447Ile	missense	Exon 3 of 3	ENSP00000266483.2
	ALG10	ENST00000541875.1	TSL:1	n.*1079G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000443142.1
	ALG10	ENST00000541875.1	TSL:1	n.*1079G>A		3_prime_UTR	Exon 3 of 3	ENSP00000443142.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461620 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111850

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome 2 Benign:1

Aug 10, 2004

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.42
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.72
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.25	N
PhyloP100		4.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.077
Sift	Benign	0.50	T
Sift4G	Benign	0.83	T
Polyphen		0.025	B
Vest4		0.16
MutPred		0.45		Gain of catalytic residue at V446 (P = 9e-04)
MVP		0.10
MPC		0.16
ClinPred		0.35	T
GERP RS		2.1
Varity_R		0.039
gMVP		0.43
Mutation Taster		=88/12	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: rs121908850; hg19: chr12-34179767;