rs34364382

chr1-95072868-C-Gchr1-95072868-C-T

Variant summary

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

The NM_144988.4(ALG14):c.31G>C(p.Ala11Pro) 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. 12/20 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. A11T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG14 NM_144988.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

ALG14 (HGNC:28287): (ALG14 UDP-N-acetylglucosaminyltransferase subunit) This gene is a member of the glycosyltransferase 1 family. The encoded protein and ALG13 are thought to be subunits of UDP-GlcNAc transferase, which catalyzes the first two committed steps in endoplasmic reticulum N-linked glycosylation. Mutations in this gene have been linked to congenital myasthenic syndrome (CMSWTA). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

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=0.27131367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG14	NM_144988.4	c.31G>C	p.Ala11Pro	missense_variant	1/4	ENST00000370205.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG14	ENST00000370205.6	c.31G>C	p.Ala11Pro	missense_variant	1/4	1	NM_144988.4	P1
ALG14	ENST00000495856.1	n.7G>C		non_coding_transcript_exon_variant	1/4	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	Uncertain	0.42
BayesDel_addAF	Benign	0.0032	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.048	D
Polyphen		0.80	P
Vest4		0.41
MutPred		0.51		Gain of loop (P = 0.0013);
MVP		0.36
MPC		0.60
ClinPred		0.57	D
GERP RS		3.3
Varity_R		0.33
gMVP		0.80

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: rs34364382; hg19: chr1-95538424;