2-135754247-A-G

Variant names:

• chr2-135754247-A-G
• rs1050115
• NM_014607.4:c.303A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_014607.4(UBXN4):​c.303A>G​(p.Glu101Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,612,732 control chromosomes in the GnomAD database, including 22,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2548 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19911 hom.)
• Consequence: UBXN4 NM_014607.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.859
• Publications: 29 publications found

Genes affected

UBXN4 (HGNC:14860): (UBX domain protein 4) UBXD2 is an integral membrane protein of the endoplasmic reticulum (ER) that binds valosin-containing protein (VCP; MIM 601023) and promotes ER-associated protein degradation (ERAD) (Liang et al., 2006 [PubMed 16968747]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-135754247-A-G is Benign according to our data. Variant chr2-135754247-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 4076127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.859 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014607.4. 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
	UBXN4	NM_014607.4	MANE Select	c.303A>G	p.Glu101Glu	synonymous	Exon 4 of 13	NP_055422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN4	ENST00000272638.14	TSL:1 MANE Select	c.303A>G	p.Glu101Glu	synonymous	Exon 4 of 13	ENSP00000272638.9
	UBXN4	ENST00000416538.5	TSL:5	n.*606A>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000391586.1
	UBXN4	ENST00000470687.1	TSL:2	n.377A>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26008 AN: 152044 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.185 AC: 46235 AN: 249322 AF XY: 0.191

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.147 AC: 214712 AN: 1460570 Hom.: 19911 Cov.: 31 AF XY: 0.153 AC XY: 110857 AN XY: 726638

African (AFR) AF: 0.151 AC: 5057 AN: 33458

American (AMR) AF: 0.189 AC: 8465 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 11309 AN: 26086

East Asian (EAS) AF: 0.153 AC: 6058 AN: 39676

South Asian (SAS) AF: 0.222 AC: 19173 AN: 86192

European-Finnish (FIN) AF: 0.136 AC: 7287 AN: 53412

Middle Eastern (MID) AF: 0.360 AC: 2074 AN: 5758

European-Non Finnish (NFE) AF: 0.130 AC: 144430 AN: 1110968

Other (OTH) AF: 0.180 AC: 10859 AN: 60338

GnomAD4 genome AF: 0.171 AC: 26022 AN: 152162 Hom.: 2548 Cov.: 32 AF XY: 0.173 AC XY: 12906 AN XY: 74392

African (AFR) AF: 0.142 AC: 5877 AN: 41498

American (AMR) AF: 0.232 AC: 3549 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1535 AN: 3470

East Asian (EAS) AF: 0.180 AC: 934 AN: 5184

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10592

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10913 AN: 68002

Other (OTH) AF: 0.244 AC: 515 AN: 2114

Alfa AF: 0.189 Hom.: 6034

Bravo AF: 0.175

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 30, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.4
DANN	Benign	0.60
PhyloP100		0.86
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1050115; hg19: chr2-136511817; COSMIC: COSV55633547; COSMIC: COSV55633547;