11-111857609-C-T

Position:

• chr11-111857609-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024740.2(ALG9):​c.694G>A​(p.Ala232Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A232P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ALG9 NM_024740.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61

Genes affected

ALG9 (HGNC:15672): (ALG9 alpha-1,2-mannosyltransferase) This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG9	NM_024740.2	c.694G>A	p.Ala232Thr	missense_variant	6/15	ENST00000616540.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG9	ENST00000616540.5	c.694G>A	p.Ala232Thr	missense_variant	6/15	1	NM_024740.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.;.;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.0	M;.;.;M;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	.;N;N;.;.
REVEL	Benign	0.27
Sift	Benign	0.16	.;T;T;.;.
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.76	P;.;.;P;.
Vest4		0.67
MutPred		0.46		Loss of helix (P = 0.1299);.;.;Loss of helix (P = 0.1299);.;
MVP		0.87
MPC		0.54
ClinPred		0.63	D
GERP RS		6.0
Varity_R		0.24
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs36111204; hg19: chr11-111728332;