rs1156822888

Positions:

• chr1-95072813-A-C
• chr1-95072813-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144988.4(ALG14):​c.86T>G​(p.Met29Arg) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M29T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG14 NM_144988.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

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]

ALG14 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043861836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG14	NM_144988.4	c.86T>G	p.Met29Arg	missense_variant	1/4	ENST00000370205.6	NP_659425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG14	ENST00000370205.6	c.86T>G	p.Met29Arg	missense_variant	1/4	1	NM_144988.4	ENSP00000359224.4
ALG14	ENST00000495856.1	n.62T>G		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	Benign	0.035
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.69
DANN	Benign	0.47
DEOGEN2	Benign	0.061	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.086	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.0090
Sift	Benign	0.42	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.42		Gain of solvent accessibility (P = 0.0078);
MVP		0.048
MPC		0.54
ClinPred		0.060	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.50

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: chr1-95538369;