NM_003344.4:c.336A>G

Variant names:

• chr7-129839298-T-C
• rs12539800
• NM_003344.4:c.336A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_003344.4(UBE2H):​c.336A>G​(p.Leu112Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0798 in 1,613,644 control chromosomes in the GnomAD database, including 5,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.064 (371 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5346 hom.)
• Consequence: UBE2H NM_003344.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.74
• Publications: 12 publications found

Genes affected

UBE2H (HGNC:12484): (ubiquitin conjugating enzyme E2 H) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein sequence is 100% identical to the mouse homolog and 98% identical to the frog and zebrafish homologs. Three alternatively spliced transcript variants have been found for this gene and they encode distinct isoforms. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 7-129839298-T-C is Benign according to our data. Variant chr7-129839298-T-C is described in ClinVar as Benign. ClinVar VariationId is 3056240.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2H	NM_003344.4	MANE Select	c.336A>G	p.Leu112Leu	synonymous	Exon 6 of 7	NP_003335.1
	UBE2H	NM_182697.3		c.243A>G	p.Leu81Leu	synonymous	Exon 4 of 5	NP_874356.1
	UBE2H	NM_001202498.2		c.126A>G	p.Leu42Leu	synonymous	Exon 6 of 7	NP_001189427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2H	ENST00000355621.8	TSL:1 MANE Select	c.336A>G	p.Leu112Leu	synonymous	Exon 6 of 7	ENSP00000347836.3
	UBE2H	ENST00000473814.6	TSL:1	c.243A>G	p.Leu81Leu	synonymous	Exon 4 of 5	ENSP00000419097.2
	UBE2H	ENST00000483368.1	TSL:1	n.444A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9665 AN: 151914 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0636

GnomAD2 exomes AF: 0.0652 AC: 16382 AN: 251304 AF XY: 0.0656

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.0398

Gnomad ASJ exome AF: 0.0248

Gnomad EAS exome AF: 0.0468

Gnomad FIN exome AF: 0.0893

Gnomad NFE exome AF: 0.0908

Gnomad OTH exome AF: 0.0691

GnomAD4 exome AF: 0.0814 AC: 119023 AN: 1461612 Hom.: 5346 Cov.: 31 AF XY: 0.0797 AC XY: 57920 AN XY: 727100

African (AFR) AF: 0.0191 AC: 639 AN: 33474

American (AMR) AF: 0.0421 AC: 1880 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 657 AN: 26132

East Asian (EAS) AF: 0.0298 AC: 1181 AN: 39680

South Asian (SAS) AF: 0.0284 AC: 2447 AN: 86226

European-Finnish (FIN) AF: 0.0839 AC: 4480 AN: 53404

Middle Eastern (MID) AF: 0.0415 AC: 239 AN: 5764

European-Non Finnish (NFE) AF: 0.0929 AC: 103348 AN: 1111868

Other (OTH) AF: 0.0688 AC: 4152 AN: 60386

GnomAD4 genome AF: 0.0636 AC: 9669 AN: 152032 Hom.: 371 Cov.: 32 AF XY: 0.0629 AC XY: 4670 AN XY: 74284

African (AFR) AF: 0.0234 AC: 970 AN: 41496

American (AMR) AF: 0.0538 AC: 821 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3464

East Asian (EAS) AF: 0.0447 AC: 231 AN: 5164

South Asian (SAS) AF: 0.0264 AC: 127 AN: 4812

European-Finnish (FIN) AF: 0.0925 AC: 974 AN: 10528

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6218 AN: 67986

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0765 Hom.: 330

Bravo AF: 0.0593

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

UBE2H-related disorder Benign:1

Mar 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		4.7
Mutation Taster		=93/7	polymorphism (auto)

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: rs12539800; hg19: chr7-129479138;