ENST00000427587:c.*891_*897delAAATAAA

Variant names:

• chr16-5084734-CTTTATTT-C
• NM_201400.4:c.*891_*897delAAATAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000427587.9(EEF2KMT):​c.*891_*897delAAATAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EEF2KMT ENST00000427587.9 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

EEF2KMT (HGNC:32221): (eukaryotic elongation factor 2 lysine methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation. Located in cytoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

ALG1 Gene-Disease associations (from GenCC):

• ALG1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-5084734-CTTTATTT-C is Benign according to our data. Variant chr16-5084734-CTTTATTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3726058.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427587.9. 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
	EEF2KMT	NM_201400.4	MANE Select	c.*891_*897delAAATAAA		3_prime_UTR	Exon 8 of 8	NP_958802.1	Q96G04-1
	ALG1	NM_019109.5	MANE Select	c.1264-12_1264-6delATTTTTT		splice_region intron	N/A	NP_061982.3
	EEF2KMT	NM_201598.4		c.*891_*897delAAATAAA		3_prime_UTR	Exon 7 of 7	NP_963892.1	Q96G04-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF2KMT	ENST00000427587.9	TSL:1 MANE Select	c.*891_*897delAAATAAA		3_prime_UTR	Exon 8 of 8	ENSP00000398502.3	Q96G04-1
	EEF2KMT	ENST00000458008.8	TSL:1	c.*891_*897delAAATAAA		3_prime_UTR	Exon 7 of 7	ENSP00000389710.3	Q96G04-2
	ALG1	ENST00000262374.10	TSL:1 MANE Select	c.1264-12_1264-6delATTTTTT		splice_region intron	N/A	ENSP00000262374.5	Q9BT22-1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	ALG1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

hg19: chr16-5134735;