16-5084551-C-G

Variant names:

• chr16-5084551-C-G
• rs114470989
• NM_201400.4:c.*1081G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201400.4(EEF2KMT):​c.*1081G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 698,648 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EEF2KMT NM_201400.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201400.4. 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
	EEF2KMT	NM_201400.4	MANE Select	c.*1081G>C		3_prime_UTR	Exon 8 of 8	NP_958802.1	Q96G04-1
	ALG1	NM_019109.5	MANE Select	c.1264-199C>G		intron	N/A	NP_061982.3
	EEF2KMT	NM_201598.4		c.*1081G>C		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.*1081G>C		3_prime_UTR	Exon 8 of 8	ENSP00000398502.3	Q96G04-1
	EEF2KMT	ENST00000458008.8	TSL:1	c.*1081G>C		3_prime_UTR	Exon 7 of 7	ENSP00000389710.3	Q96G04-2
	ALG1	ENST00000262374.10	TSL:1 MANE Select	c.1264-199C>G		intron	N/A	ENSP00000262374.5	Q9BT22-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 1 AN: 698648 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 361306

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18108

American (AMR) AF: 0.00 AC: 0 AN: 30828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17870

East Asian (EAS) AF: 0.00 AC: 0 AN: 32358

South Asian (SAS) AF: 0.00 AC: 0 AN: 56524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2640

European-Non Finnish (NFE) AF: 0.00000211 AC: 1 AN: 474028

Other (OTH) AF: 0.00 AC: 0 AN: 34958

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.53
PhyloP100		-2.7

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

Other links and lift over

dbSNP: rs114470989; hg19: chr16-5134552;