rs28661796

Variant names:

• chr16-5084598-G-C
• rs28661796
• NM_201400.4:c.*1034C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_201400.4(EEF2KMT):​c.*1034C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,203,186 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (7 hom.)
• Consequence: EEF2KMT NM_201400.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-5084598-G-C is Benign according to our data. Variant chr16-5084598-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1213047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0053 (807/152310) while in subpopulation AFR AF = 0.0186 (775/41560). AF 95% confidence interval is 0.0176. There are 7 homozygotes in GnomAd4. There are 371 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.*1034C>G		3_prime_UTR	Exon 8 of 8	NP_958802.1	Q96G04-1
	ALG1	NM_019109.5	MANE Select	c.1264-152G>C		intron	N/A	NP_061982.3
	EEF2KMT	NM_201598.4		c.*1034C>G		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.*1034C>G		3_prime_UTR	Exon 8 of 8	ENSP00000398502.3	Q96G04-1
	EEF2KMT	ENST00000458008.8	TSL:1	c.*1034C>G		3_prime_UTR	Exon 7 of 7	ENSP00000389710.3	Q96G04-2
	ALG1	ENST00000262374.10	TSL:1 MANE Select	c.1264-152G>C		intron	N/A	ENSP00000262374.5	Q9BT22-1

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 807 AN: 152192 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000562 AC: 591 AN: 1050876 Hom.: 7 Cov.: 15 AF XY: 0.000453 AC XY: 241 AN XY: 531498

African (AFR) AF: 0.0195 AC: 489 AN: 25014

American (AMR) AF: 0.000943 AC: 33 AN: 34984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22738

East Asian (EAS) AF: 0.00 AC: 0 AN: 34722

South Asian (SAS) AF: 0.0000138 AC: 1 AN: 72652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34198

Middle Eastern (MID) AF: 0.000583 AC: 2 AN: 3430

European-Non Finnish (NFE) AF: 0.0000103 AC: 8 AN: 776312

Other (OTH) AF: 0.00124 AC: 58 AN: 46826

GnomAD4 genome AF: 0.00530 AC: 807 AN: 152310 Hom.: 7 Cov.: 33 AF XY: 0.00498 AC XY: 371 AN XY: 74482

African (AFR) AF: 0.0186 AC: 775 AN: 41560

American (AMR) AF: 0.00163 AC: 25 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00423 Hom.: 2

Bravo AF: 0.00632

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.44
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism

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: rs28661796; hg19: chr16-5134599;