7-129835045-G-A

Variant names:

• chr7-129835045-G-A
• rs375884538
• NM_003344.4:c.444C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_003344.4(UBE2H):​c.444C>T​(p.Tyr148Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: UBE2H NM_003344.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.02
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-129835045-G-A is Benign according to our data. Variant chr7-129835045-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3058312.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 13 AD gene.

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.444C>T	p.Tyr148Tyr	synonymous	Exon 7 of 7	NP_003335.1	P62256-1
	UBE2H	NM_182697.3		c.351C>T	p.Tyr117Tyr	synonymous	Exon 5 of 5	NP_874356.1	P62256-2
	UBE2H	NM_001202498.2		c.234C>T	p.Tyr78Tyr	synonymous	Exon 7 of 7	NP_001189427.1	A0A3B3IU20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2H	ENST00000355621.8	TSL:1 MANE Select	c.444C>T	p.Tyr148Tyr	synonymous	Exon 7 of 7	ENSP00000347836.3	P62256-1
	UBE2H	ENST00000473814.6	TSL:1	c.351C>T	p.Tyr117Tyr	synonymous	Exon 5 of 5	ENSP00000419097.2	P62256-2
	UBE2H	ENST00000483368.1	TSL:1	n.552C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251396 AF XY: 0.0000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000125 AC: 182 AN: 1461840 Hom.: 0 Cov.: 30 AF XY: 0.000120 AC XY: 87 AN XY: 727218

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000138 AC: 154 AN: 1111988

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74276

African (AFR) AF: 0.0000483 AC: 2 AN: 41386

American (AMR) AF: 0.000131 AC: 2 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.000125

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UBE2H-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs375884538; hg19: chr7-129474885; COSMIC: COSV62920030; COSMIC: COSV62920030;