3-184243878-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005787.6(ALG3):​c.845C>G​(p.Ala282Gly) 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. 15/21 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3105462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG3	NM_005787.6	c.845C>G	p.Ala282Gly	missense_variant	Exon 6 of 9	ENST00000397676.8	NP_005778.1
ALG3	NM_001006941.2	c.701C>G	p.Ala234Gly	missense_variant	Exon 6 of 9		NP_001006942.1
ALG3	NR_024533.1	n.776C>G		non_coding_transcript_exon_variant	Exon 5 of 8
ALG3	NR_024534.1	n.839C>G		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>G	p.Ala282Gly	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	0.082
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;.
Eigen	Benign	-0.011
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.080	T;T;D
Polyphen		0.15	B;.;B
Vest4		0.18
MutPred		0.54		Loss of stability (P = 0.0178);.;.;
MVP		0.94
MPC		0.11
ClinPred		0.42	T
GERP RS		4.7
Varity_R		0.057
gMVP		0.32

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: chr3-183961666; COSMIC: COSV99063190; COSMIC: COSV99063190;