chr12-93410717-G-A

Variant names:

• chr12-93410717-G-A
• rs7969431
• NM_003348.4:c.418+17C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003348.4(UBE2N):​c.418+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,613,750 control chromosomes in the GnomAD database, including 311 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 0.014 (24 hom., cov: 33)
  • Exomes 𝑓: 0.017 (287 hom.)
• Consequence: UBE2N NM_003348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 6 publications found

Genes affected

UBE2N (HGNC:12492): (ubiquitin conjugating enzyme E2 N) 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. Studies in mouse suggest that this protein plays a role in DNA postreplication repair. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2194/152334) while in subpopulation NFE AF = 0.0187 (1269/68040). AF 95% confidence interval is 0.0178. There are 24 homozygotes in GnomAd4. There are 1089 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2194 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003348.4. 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
	UBE2N	NM_003348.4	MANE Select	c.418+17C>T		intron	N/A	NP_003339.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2N	ENST00000318066.7	TSL:1 MANE Select	c.418+17C>T		intron	N/A	ENSP00000316176.2
	UBE2N	ENST00000550657.1	TSL:2	c.*154C>T		3_prime_UTR	Exon 2 of 2	ENSP00000449352.1
	UBE2N	ENST00000552442.1	TSL:5	c.277+336C>T		intron	N/A	ENSP00000448352.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2195 AN: 152216 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00376

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0150 AC: 3756 AN: 250860 AF XY: 0.0152

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0224

Gnomad NFE exome AF: 0.0196

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0169 AC: 24771 AN: 1461416 Hom.: 287 Cov.: 31 AF XY: 0.0169 AC XY: 12302 AN XY: 726972

African (AFR) AF: 0.00332 AC: 111 AN: 33468

American (AMR) AF: 0.0126 AC: 562 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 709 AN: 26114

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00717 AC: 618 AN: 86242

European-Finnish (FIN) AF: 0.0219 AC: 1170 AN: 53404

Middle Eastern (MID) AF: 0.0340 AC: 196 AN: 5764

European-Non Finnish (NFE) AF: 0.0183 AC: 20356 AN: 1111654

Other (OTH) AF: 0.0173 AC: 1047 AN: 60372

GnomAD4 genome AF: 0.0144 AC: 2194 AN: 152334 Hom.: 24 Cov.: 33 AF XY: 0.0146 AC XY: 1089 AN XY: 74486

African (AFR) AF: 0.00375 AC: 156 AN: 41570

American (AMR) AF: 0.0164 AC: 251 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4832

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0187 AC: 1269 AN: 68040

Other (OTH) AF: 0.0199 AC: 42 AN: 2110

Alfa AF: 0.0170 Hom.: 7

Bravo AF: 0.0136

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.69
PhyloP100		0.12
Mutation Taster		=99/1	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: rs7969431; hg19: chr12-93804493;