12-38318352-A-C

Variant names:

• chr12-38318352-A-C
• rs139511694
• NM_001013620.4:c.263A>C

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.263A>C​(p.His88Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H88R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALG10B NM_001013620.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995
• 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=0.10336974).

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.263A>C	p.His88Pro	missense	Exon 2 of 3	NP_001013642.2	Q5I7T1
	ALG10B	NM_001308340.2		c.263A>C	p.His88Pro	missense	Exon 2 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.263A>C	p.His88Pro	missense	Exon 2 of 3	ENSP00000310120.4	Q5I7T1
	ALG10B	ENST00000548240.1	TSL:1	n.*3A>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000449210.1	F8VWA9
	ALG10B	ENST00000548240.1	TSL:1	n.*3A>C		3_prime_UTR	Exon 2 of 3	ENSP00000449210.1	F8VWA9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461820 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.12	N
PhyloP100		0.99
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.24
Sift	Benign	0.28	T
Sift4G	Benign	0.34	T
Polyphen		0.022	B
Vest4		0.30
MutPred		0.39		Gain of catalytic residue at A84 (P = 0)
MVP		0.42
MPC		0.058
ClinPred		0.18	T
GERP RS		3.7
Varity_R		0.35
gMVP		0.77
Mutation Taster		=74/26	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: rs139511694; hg19: chr12-38712154;