10-44977783-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_007021.4(DEPP1):c.248G>A(p.Arg83Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,601,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: DEPP1 NM_007021.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.826

Genes affected

DEPP1 (HGNC:23355): (DEPP autophagy regulator 1) The expression of this gene is induced by fasting as well as by progesterone. The protein encoded by this gene contains a t-synaptosome-associated protein receptor (SNARE) coiled-coil homology domain and a peroxisomal targeting signal. Production of the encoded protein leads to phosphorylation and activation of the transcription factor ELK1. [provided by RefSeq, Jul 2008]

RASSF4 (HGNC:20793): (Ras association domain family member 4) The function of this gene has not yet been determined but may involve a role in tumor suppression. Alternative splicing of this gene results in several transcript variants; however, most of the variants have not been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.007753074).
• BP6: Variant 10-44977783-C-T is Benign according to our data. Variant chr10-44977783-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3081757.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPP1	NM_007021.4	c.248G>A	p.Arg83Gln	missense_variant	2/2	ENST00000298295.4
RASSF4	NM_032023.4	c.139-4738C>T		intron_variant		ENST00000340258.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPP1	ENST00000298295.4	c.248G>A	p.Arg83Gln	missense_variant	2/2	1	NM_007021.4	P1
RASSF4	ENST00000340258.10	c.139-4738C>T		intron_variant		1	NM_032023.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000525 AC: 8 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000106 AC: 26 AN: 244446 Hom.: 0 AF XY: 0.0000904 AC XY: 12 AN XY: 132706

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000153

Gnomad ASJ exome AF: 0.00157

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000451

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000483 AC: 70 AN: 1448930 Hom.: 0 Cov.: 31 AF XY: 0.0000473 AC XY: 34 AN XY: 719128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000117

Gnomad4 ASJ exome AF: 0.00132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000163

Gnomad4 OTH exome AF: 0.000134

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74378

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 05, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.23
Dann	Benign	0.79
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.0078	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	1.2	N;N
REVEL	Benign	0.0060
Sift	Benign	0.89	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0090	B;.
Vest4		0.015
MVP		0.15
MPC		0.12
ClinPred		0.017	T
GERP RS		-2.7
Varity_R		0.016
gMVP		0.036

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: rs149139243; hg19: chr10-45473231;