NM_001013620.4:c.799T>C

Variant names:

• chr12-38320590-T-C
• NM_001013620.4:c.799T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001013620.4(ALG10B):​c.799T>C​(p.Phe267Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG10B NM_001013620.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

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.799T>C	p.Phe267Leu	missense	Exon 3 of 3	NP_001013642.2	Q5I7T1
	ALG10B	NM_001308340.2		c.369+2132T>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.799T>C	p.Phe267Leu	missense	Exon 3 of 3	ENSP00000310120.4	Q5I7T1
	ALG10B	ENST00000548240.1	TSL:1	n.*539T>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000449210.1	F8VWA9
	ALG10B	ENST00000548240.1	TSL:1	n.*539T>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

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		7.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.76		Gain of catalytic residue at V269 (P = 0)
MVP		0.77
MPC		0.32
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.91
gMVP		0.91
Mutation Taster		=36/64	disease causing

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

hg19: chr12-38714392;