12-38320590-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG10B	NM_001013620.4	c.799T>C	p.Phe267Leu	missense_variant	Exon 3 of 3	ENST00000308742.9	NP_001013642.2
ALG10B	XM_005268665.5	c.619T>C	p.Phe207Leu	missense_variant	Exon 3 of 3		XP_005268722.1
ALG10B	NM_001308340.2	c.369+2132T>C		intron_variant	Intron 2 of 2		NP_001295269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG10B	ENST00000308742.9	c.799T>C	p.Phe267Leu	missense_variant	Exon 3 of 3	1	NM_001013620.4	ENSP00000310120.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.799T>C (p.F267L) alteration is located in exon 3 (coding exon 3) of the ALG10B gene. This alteration results from a T to C substitution at nucleotide position 799, causing the phenylalanine (F) at amino acid position 267 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-38714392;