chr8-120001564-A-G

Position:

• chr8-120001564-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022783.4(DEPTOR):​c.644A>G​(p.Tyr215Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPTOR NM_022783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPTOR	NM_022783.4	c.644A>G	p.Tyr215Cys	missense_variant	5/9	ENST00000286234.6
DEPTOR	NM_001283012.2	c.341A>G	p.Tyr114Cys	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPTOR	ENST00000286234.6	c.644A>G	p.Tyr215Cys	missense_variant	5/9	1	NM_022783.4	P1
DEPTOR	ENST00000523492.5	c.341A>G	p.Tyr114Cys	missense_variant	3/7	2
DEPTOR	ENST00000518057.1	n.93A>G		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 18, 2023

The c.644A>G (p.Y215C) alteration is located in exon 5 (coding exon 5) of the DEPTOR gene. This alteration results from a A to G substitution at nucleotide position 644, causing the tyrosine (Y) at amino acid position 215 to be replaced by a cysteine (C). 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	Benign	0.27
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.015	D
MutationAssessor	Pathogenic	3.1	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.016	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.72	.;P
Vest4		0.81
MutPred		0.76		.;Gain of disorder (P = 0.0373);
MVP		0.88
MPC		0.34
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.61
gMVP		0.80

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: chr8-121013803;