16-5084551-C-T

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

2

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]
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]

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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
EEF2KMTNM_201400.4 linkc.*1081G>A 3_prime_UTR_variant Exon 8 of 8 ENST00000427587.9 NP_958802.1
ALG1NM_019109.5 linkc.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
EEF2KMTENST00000427587 linkc.*1081G>A 3_prime_UTR_variant Exon 8 of 8 1 NM_201400.4 ENSP00000398502.3 Q96G04-1
ALG1ENST00000262374.10 linkc.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.:
39
Cov.:
33
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.:
28
Cov.:
9
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.:
38
Cov.:
33
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.:
4
Bravo
AF:
0.0143
Asia WGS
AF:
0.00173
AC:
6
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.

Other links and lift over

dbSNP: rs114470989; hg19: chr16-5134552; API