rs2391388

Positions:

• chr1-95020269-A-C
• chr1-95020269-A-G
• chr1-95020269-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144988.4(ALG14):​c.420+6860T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,840 control chromosomes in the GnomAD database, including 18,843 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18843 hom., cov: 30)
• Consequence: ALG14 NM_144988.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG14	NM_144988.4	c.420+6860T>G		intron_variant		ENST00000370205.6	NP_659425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG14	ENST00000370205.6	c.420+6860T>G		intron_variant		1	NM_144988.4	ENSP00000359224	P1
ALG14	ENST00000507727.2	n.75+6860T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74441 AN: 151722 Hom.: 18829 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.491 AC: 74502 AN: 151840 Hom.: 18843 Cov.: 30 AF XY: 0.488 AC XY: 36234 AN XY: 74228

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.524

Alfa AF: 0.466 Hom.: 3993

Bravo AF: 0.507

Asia WGS AF: 0.672 AC: 2334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.44

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: rs2391388; hg19: chr1-95485825;