1-202333104-A-G

Variant names:

• chr1-202333104-A-G
• rs17490864
• NM_014176.4:c.385-11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014176.4(UBE2T):​c.385-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,611,924 control chromosomes in the GnomAD database, including 10,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (628 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9972 hom.)
• Consequence: UBE2T NM_014176.4 intron
• Scores: Splicing: ADA: 0.04316
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.880
• Publications: 10 publications found

Genes affected

UBE2T (HGNC:25009): (ubiquitin conjugating enzyme E2 T) The protein encoded by this gene catalyzes the covalent attachment of ubiquitin to protein substrates. Defects in this gene have been associated with Fanconi anemia of complementation group T. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

UBE2T Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group T

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-202333104-A-G is Benign according to our data. Variant chr1-202333104-A-G is described in ClinVar as Benign. ClinVar VariationId is 1231134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014176.4. 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
	UBE2T	NM_014176.4	MANE Select	c.385-11T>C		intron	N/A	NP_054895.1	Q9NPD8
	UBE2T	NM_001310326.2		c.295-11T>C		intron	N/A	NP_001297255.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2T	ENST00000646651.1	MANE Select	c.385-11T>C		intron	N/A	ENSP00000494957.1	Q9NPD8
	UBE2T	ENST00000934402.1		c.424-11T>C		intron	N/A	ENSP00000604461.1
	UBE2T	ENST00000699423.1		c.385-11T>C		intron	N/A	ENSP00000514379.1	Q9NPD8

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11912 AN: 151930 Hom.: 629 Cov.: 31

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0614

GnomAD2 exomes AF: 0.0765 AC: 19237 AN: 251318 AF XY: 0.0771

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.0391

Gnomad ASJ exome AF: 0.0477

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0959

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.0781

GnomAD4 exome AF: 0.108 AC: 157499 AN: 1459876 Hom.: 9972 Cov.: 31 AF XY: 0.105 AC XY: 76477 AN XY: 726484

African (AFR) AF: 0.0172 AC: 575 AN: 33442

American (AMR) AF: 0.0421 AC: 1881 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 1240 AN: 26122

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39692

South Asian (SAS) AF: 0.0158 AC: 1363 AN: 86226

European-Finnish (FIN) AF: 0.0967 AC: 5167 AN: 53416

Middle Eastern (MID) AF: 0.0149 AC: 86 AN: 5768

European-Non Finnish (NFE) AF: 0.128 AC: 141948 AN: 1110166

Other (OTH) AF: 0.0868 AC: 5233 AN: 60322

GnomAD4 genome AF: 0.0783 AC: 11907 AN: 152048 Hom.: 628 Cov.: 31 AF XY: 0.0753 AC XY: 5594 AN XY: 74324

African (AFR) AF: 0.0225 AC: 933 AN: 41478

American (AMR) AF: 0.0613 AC: 935 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4818

European-Finnish (FIN) AF: 0.0991 AC: 1045 AN: 10542

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8512 AN: 67982

Other (OTH) AF: 0.0607 AC: 128 AN: 2108

Alfa AF: 0.0995 Hom.: 2410

Bravo AF: 0.0732

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Fanconi anemia complementation group T (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.043
dbscSNV1_RF	Benign	0.31
SpliceAI score (max)		0.040		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: rs17490864; hg19: chr1-202302232;