7-129857658-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2H	NM_003344.4	c.246-95G>A		intron_variant	Intron 4 of 6	ENST00000355621.8	NP_003335.1
UBE2H	NM_182697.3	c.206-18323G>A		intron_variant	Intron 3 of 4		NP_874356.1
UBE2H	NM_001202498.2	c.36-95G>A		intron_variant	Intron 4 of 6		NP_001189427.1
UBE2H	XM_047420796.1	c.36-95G>A		intron_variant	Intron 5 of 7		XP_047276752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2H	ENST00000355621.8	c.246-95G>A		intron_variant	Intron 4 of 6	1	NM_003344.4	ENSP00000347836.3

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

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0455

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.0289

Gnomad4 SAS exome AF: 0.0288

Gnomad4 FIN exome AF: 0.0846

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.0700

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

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.0450

Gnomad4 SAS AF: 0.0266

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0191 Hom.: 10

Bravo AF: 0.0594

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs718925; hg19: chr7-129497498;