NM_003344.4:c.246-95G>A

Variant names:

• chr7-129857658-C-T
• rs718925
• NM_003344.4:c.246-95G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003344.4(UBE2H):​c.246-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,292,154 control chromosomes in the GnomAD database, including 4,619 homozygotes. 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: 𝑓 0.064 (372 hom., cov: 32)
  • Exomes 𝑓: 0.081 (4247 hom.)
• Consequence: UBE2H NM_003344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2H	NM_003344.4	MANE Select	c.246-95G>A		intron	N/A	NP_003335.1
	UBE2H	NM_182697.3		c.206-18323G>A		intron	N/A	NP_874356.1
	UBE2H	NM_001202498.2		c.36-95G>A		intron	N/A	NP_001189427.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2H	ENST00000355621.8	TSL:1 MANE Select	c.246-95G>A		intron	N/A	ENSP00000347836.3
	UBE2H	ENST00000473814.6	TSL:1	c.206-18323G>A		intron	N/A	ENSP00000419097.2
	UBE2H	ENST00000871229.1		c.246-95G>A		intron	N/A	ENSP00000541288.1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9695 AN: 152004 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.0812 AC: 92528 AN: 1140032 Hom.: 4247 AF XY: 0.0795 AC XY: 45921 AN XY: 577482

African (AFR) AF: 0.0193 AC: 485 AN: 25066

American (AMR) AF: 0.0455 AC: 1470 AN: 32298

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 546 AN: 21438

East Asian (EAS) AF: 0.0289 AC: 1069 AN: 36942

South Asian (SAS) AF: 0.0288 AC: 2013 AN: 69864

European-Finnish (FIN) AF: 0.0846 AC: 4310 AN: 50960

Middle Eastern (MID) AF: 0.0423 AC: 193 AN: 4566

European-Non Finnish (NFE) AF: 0.0930 AC: 79012 AN: 849928

Other (OTH) AF: 0.0700 AC: 3430 AN: 48970

GnomAD4 genome AF: 0.0638 AC: 9699 AN: 152122 Hom.: 372 Cov.: 32 AF XY: 0.0630 AC XY: 4685 AN XY: 74360

African (AFR) AF: 0.0237 AC: 982 AN: 41496

American (AMR) AF: 0.0538 AC: 822 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3466

East Asian (EAS) AF: 0.0450 AC: 233 AN: 5182

South Asian (SAS) AF: 0.0266 AC: 128 AN: 4818

European-Finnish (FIN) AF: 0.0931 AC: 983 AN: 10554

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0915 AC: 6223 AN: 68006

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0193 Hom.: 11

Bravo AF: 0.0594

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.52
PhyloP100		-0.16
Mutation Taster		=100/0	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: rs718925; hg19: chr7-129497498;