12-38320572-G-C

Variant names:

• chr12-38320572-G-C
• NM_001013620.4:c.781G>C
• ALG10B p.Gly261Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001013620.4(ALG10B):​c.781G>C​(p.Gly261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG10B NM_001013620.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34433725).

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.781G>C	p.Gly261Arg	missense	Exon 3 of 3	NP_001013642.2	Q5I7T1
	ALG10B	NM_001308340.2		c.369+2114G>C		intron	N/A	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.781G>C	p.Gly261Arg	missense	Exon 3 of 3	ENSP00000310120.4	Q5I7T1
	ALG10B	ENST00000548240.1	TSL:1	n.*521G>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000449210.1	F8VWA9
	ALG10B	ENST00000548240.1	TSL:1	n.*521G>C		3_prime_UTR	Exon 3 of 3	ENSP00000449210.1	F8VWA9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Uncertain	0.025	D
Sift4G	Benign	0.15	T
Varity_R		0.32
gMVP		0.84
Mutation Taster		=93/7	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-38714374;