Genetic Variant EEF2KMT:c.*1081G>A (chr16-5084551-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_201400.4(EEF2KMT):c.*1081G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 850,854 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 28 hom. )

Consequence

EEF2KMT
NM_201400.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.67

Variant links:

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]

EEF2KMT links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 16-5084551-C-T is Benign according to our data. Variant chr16-5084551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1933/152218) while in subpopulation AFR AF= 0.0445 (1848/41512). AF 95% confidence interval is 0.0428. There are 38 homozygotes in gnomad4. There are 896 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF2KMT	NM_201400.4 link	c.*1081G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000427587.9	NP_958802.1
ALG1	NM_019109.5 link	c.1264-199C>T		intron_variant	Intron 12 of 12	ENST00000262374.10	NP_061982.3	Q9BT22-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF2KMT	ENST00000427587 link	c.*1081G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_201400.4	ENSP00000398502.3		Q96G04-1
ALG1	ENST00000262374.10 link	c.1264-199C>T		intron_variant	Intron 12 of 12	1	NM_019109.5	ENSP00000262374.5		Q9BT22-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1931

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0446

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00910

GnomAD4 exome

AF:

0.00162

AC:

1135

AN:

698636

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

486

AN XY:

361296

show subpopulations

Gnomad4 AFR exome

AF:

0.0483

Gnomad4 AMR exome

AF:

0.00269

Gnomad4 ASJ exome

AF:

0.000112

Gnomad4 EAS exome

AF:

0.000124

Gnomad4 SAS exome

AF:

0.0000531

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.0127

AC:

1933

AN:

152218

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

896

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0445

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00999

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 25, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.6

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over