chr12-57609093-C-T

Position:

• chr12-57609093-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178502.4(DTX3):​c.985C>T​(p.Pro329Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTX3 NM_178502.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

Genes affected

DTX3 (HGNC:24457): (deltex E3 ubiquitin ligase 3) DTX3 functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30288896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX3	NM_178502.4	c.985C>T	p.Pro329Ser	missense_variant	7/7	ENST00000337737.8	NP_848597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX3	ENST00000337737.8	c.985C>T	p.Pro329Ser	missense_variant	7/7	2	NM_178502.4	ENSP00000338050.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.985C>T (p.P329S) alteration is located in exon 7 (coding exon 4) of the DTX3 gene. This alteration results from a C to T substitution at nucleotide position 985, causing the proline (P) at amino acid position 329 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;T;T;.
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	.;.;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L;L;L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.7	D;D;D;D
REVEL	Benign	0.16
Sift	Benign	0.056	T;T;T;T
Sift4G	Uncertain	0.031	.;.;.;D
Polyphen		0.25	B;B;B;.
Vest4		0.45
MutPred		0.48		Gain of catalytic residue at D328 (P = 0.0012);Gain of catalytic residue at D328 (P = 0.0012);Gain of catalytic residue at D328 (P = 0.0012);.;
MVP		0.47
MPC		1.5
ClinPred		0.88	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-58002876;