1-95064932-ATC-GTT

Variant names:

• chr1-95064932-ATC-GTT
• NM_144988.4:c.220_222delGATinsAAC
• ALG14 p.Asp74Asn

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PS1_Moderate

The NM_144988.4(ALG14):​c.220_222delGATinsAAC​(p.Asp74Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D74E) 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: 6.81
• Publications: 0 publications found

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]

CNN3-DT (HGNC:54176): (CNN3 divergent transcript)

ALG14-AS1 (HGNC:41192): (ALG14 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PS1: Transcript NM_144988.4 (ALG14) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144988.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG14	NM_144988.4	MANE Select	c.220_222delGATinsAAC	p.Asp74Asn	missense	N/A	NP_659425.1	Q96F25
	ALG14	NM_001305242.2		c.220_222delGATinsAAC	p.Asp74Asn	missense	N/A	NP_001292171.1
	ALG14	NR_131032.2		n.189+7829_189+7831delGATinsAAC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG14	ENST00000370205.6	TSL:1 MANE Select	c.220_222delGATinsAAC	p.Asp74Asn	missense	N/A	ENSP00000359224.4	Q96F25
	ALG14	ENST00000897799.1		c.220_222delGATinsAAC	p.Asp74Asn	missense	N/A	ENSP00000567858.1
	ALG14	ENST00000495856.1	TSL:3	n.196_198delGATinsAAC		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-95530488;