12-113077995-A-G

Position:

• chr12-113077995-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004416.3(DTX1):​c.831A>G​(p.Pro277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000084 in 1,083,494 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: DTX1 NM_004416.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240

Genes affected

DTX1 (HGNC:3060): (deltex E3 ubiquitin ligase 1) Studies in Drosophila have identified this gene as encoding a positive regulator of the Notch-signaling pathway. The human gene encodes a protein of unknown function; however, it may play a role in basic helix-loop-helix transcription factor activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-113077995-A-G is Benign according to our data. Variant chr12-113077995-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.024 with no splicing effect.
• BS2: High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX1	NM_004416.3	c.831A>G	p.Pro277=	synonymous_variant	3/10	ENST00000548759.2	NP_004407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX1	ENST00000548759.2	c.831A>G	p.Pro277=	synonymous_variant	3/10	2	NM_004416.3	ENSP00000510707	P1
DTX1	ENST00000257600.3	c.831A>G	p.Pro277=	synonymous_variant	2/9	1		ENSP00000257600	P1

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 16 AN: 147192 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000115

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0000754

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000812 AC: 76 AN: 936194 Hom.: 0 Cov.: 31 AF XY: 0.0000661 AC XY: 29 AN XY: 439026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000148

Gnomad4 SAS exome AF: 0.0000549

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000834

Gnomad4 OTH exome AF: 0.000119

GnomAD4 genome AF: 0.000102 AC: 15 AN: 147300 Hom.: 0 Cov.: 31 AF XY: 0.000111 AC XY: 8 AN XY: 71778

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.000135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000115

Gnomad4 NFE AF: 0.0000603

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

DTX1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.30

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: rs972390216; hg19: chr12-113515800;