rs6675668

chr1-95050081-T-G

Variant summary

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

The NM_144988.4(ALG14):c.288+14785A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,994 control chromosomes in the GnomAD database, including 15,014 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 0.43 (15014 hom., cov: 31)
• Consequence: ALG14 NM_144988.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG14	NM_144988.4	c.288+14785A>C		intron_variant		ENST00000370205.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG14	ENST00000370205.6	c.288+14785A>C		intron_variant		1	NM_144988.4	P1
ALG14	ENST00000495856.1	n.265-8469A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64908 AN: 151878 Hom.: 15012 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.427 AC: 64933 AN: 151994 Hom.: 15014 Cov.: 31 AF XY: 0.431 AC XY: 32020 AN XY: 74278

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.402

Alfa AF: 0.484 Hom.: 29996

Bravo AF: 0.405

Asia WGS AF: 0.279 AC: 973 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.3
Dann	Benign	0.71

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: rs6675668; hg19: chr1-95515637;