12-38316940-C-G

Variant names:

• chr12-38316940-C-G
• rs752360964
• NM_001013620.4:c.47C>G

Variant summary

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

The NM_001013620.4(ALG10B):​c.47C>G​(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,288 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 Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ALG10B NM_001013620.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

ALG10B (HGNC:31088): (ALG10 alpha-1,2-glucosyltransferase B) Enables transferase activity. Involved in positive regulation of inward rectifier potassium channel activity; positive regulation of protein glycosylation; and protein glycosylation. Located in endoplasmic reticulum. Implicated in long QT syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]

ALG10B Gene-Disease associations (from GenCC):

• long QT syndrome 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000301992 (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=0.11382568).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013620.4. 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
	ALG10B	NM_001013620.4	MANE Select	c.47C>G	p.Thr16Ser	missense	Exon 1 of 3	NP_001013642.2	Q5I7T1
	ALG10B	NM_001308340.2		c.47C>G	p.Thr16Ser	missense	Exon 1 of 3	NP_001295269.2	F8VXJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG10B	ENST00000308742.9	TSL:1 MANE Select	c.47C>G	p.Thr16Ser	missense	Exon 1 of 3	ENSP00000310120.4	Q5I7T1
	ALG10B	ENST00000548240.1	TSL:1	n.47C>G		non_coding_transcript_exon	Exon 1 of 3	ENSP00000449210.1	F8VWA9
	ALG10B	ENST00000551464.1	TSL:3	c.47C>G	p.Thr16Ser	missense	Exon 1 of 3	ENSP00000448819.1	F8VXJ0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.090
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.048
Sift	Benign	0.33	T
Sift4G	Benign	0.41	T
Polyphen		0.15	B
Vest4		0.27
MutPred		0.35		Gain of catalytic residue at V19 (P = 0)
MVP		0.43
MPC		0.044
ClinPred		0.19	T
GERP RS		3.6
PromoterAI		-0.038	Neutral
Varity_R		0.081
gMVP		0.40
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752360964; hg19: chr12-38710742;