chr8-120003051-T-C

Position:

• chr8-120003051-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022783.4(DEPTOR):​c.865T>C​(p.Tyr289His) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DEPTOR NM_022783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.63

Genes affected

DEPTOR (HGNC:22953): (DEP domain containing MTOR interacting protein) Involved in several processes, including negative regulation of TOR signaling; negative regulation of cell size; and negative regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPTOR	NM_022783.4	c.865T>C	p.Tyr289His	missense_variant	6/9	ENST00000286234.6
DEPTOR	NM_001283012.2	c.562T>C	p.Tyr188His	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPTOR	ENST00000286234.6	c.865T>C	p.Tyr289His	missense_variant	6/9	1	NM_022783.4	P1
DEPTOR	ENST00000523492.5	c.562T>C	p.Tyr188His	missense_variant	4/7	2
DEPTOR	ENST00000518057.1	n.314T>C		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459794 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 29

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

Sep 07, 2022

The c.865T>C (p.Y289H) alteration is located in exon 6 (coding exon 6) of the DEPTOR gene. This alteration results from a T to C substitution at nucleotide position 865, causing the tyrosine (Y) at amino acid position 289 to be replaced by a histidine (H). 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	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.10
Sift	Benign	0.43	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.98	.;D
Vest4		0.68
MutPred		0.24		.;Loss of phosphorylation at Y289 (P = 0.0379);
MVP		0.69
MPC		0.64
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.18
gMVP		0.58

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: chr8-121015290;