NM_005787.6:c.845C>A

Variant names:

• chr3-184243878-G-T
• NM_005787.6:c.845C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005787.6(ALG3):​c.845C>A​(p.Ala282Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG3 NM_005787.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

ALG3 (HGNC:23056): (ALG3 alpha-1,3- mannosyltransferase) This gene encodes a member of the ALG3 family. The encoded protein catalyses the addition of the first dol-P-Man derived mannose in an alpha 1,3 linkage to Man5GlcNAc2-PP-Dol. Defects in this gene have been associated with congenital disorder of glycosylation type Id (CDG-Id) characterized by abnormal N-glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10961416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG3	NM_005787.6	c.845C>A	p.Ala282Glu	missense_variant	Exon 6 of 9	ENST00000397676.8	NP_005778.1
ALG3	NM_001006941.2	c.701C>A	p.Ala234Glu	missense_variant	Exon 6 of 9		NP_001006942.1
ALG3	NR_024533.1	n.776C>A		non_coding_transcript_exon_variant	Exon 5 of 8
ALG3	NR_024534.1	n.839C>A		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG3	ENST00000397676.8	c.845C>A	p.Ala282Glu	missense_variant	Exon 6 of 9	1	NM_005787.6	ENSP00000380793.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.22	T;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-1.8	N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	3.3	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.12
MutPred		0.51		Loss of helix (P = 0.0558);.;.;
MVP		0.87
MPC		0.099
ClinPred		0.16	T
GERP RS		4.7
Varity_R		0.052
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr3-183961666;