10-44977730-T-C

Position:

• chr10-44977730-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_007021.4(DEPP1):​c.301A>G​(p.Thr101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,609,868 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00081 (14 hom.)
• Consequence: DEPP1 NM_007021.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.458

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024353266).
• BP6: Variant 10-44977730-T-C is Benign according to our data. Variant chr10-44977730-T-C is described in ClinVar as [Benign]. Clinvar id is 786154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0067 (1020/152344) while in subpopulation AFR AF= 0.022 (916/41590). AF 95% confidence interval is 0.0208. There are 9 homozygotes in gnomad4. There are 465 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPP1	NM_007021.4	c.301A>G	p.Thr101Ala	missense_variant	2/2	ENST00000298295.4	NP_008952.1
RASSF4	NM_032023.4	c.139-4791T>C		intron_variant		ENST00000340258.10	NP_114412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPP1	ENST00000298295.4	c.301A>G	p.Thr101Ala	missense_variant	2/2	1	NM_007021.4	ENSP00000298295	P1
RASSF4	ENST00000340258.10	c.139-4791T>C		intron_variant		1	NM_032023.4	ENSP00000339692	P1

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 1017 AN: 152226 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00170 AC: 421 AN: 248360 Hom.: 5 AF XY: 0.00123 AC XY: 165 AN XY: 134690

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000814 AC: 1187 AN: 1457524 Hom.: 14 Cov.: 31 AF XY: 0.000709 AC XY: 514 AN XY: 724798

Gnomad4 AFR exome AF: 0.0254

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000813

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000928

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.00670 AC: 1020 AN: 152344 Hom.: 9 Cov.: 33 AF XY: 0.00624 AC XY: 465 AN XY: 74496

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00276 Hom.: 2

Bravo AF: 0.00805

ESP6500AA AF: 0.0227 AC: 100

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00225 AC: 273

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 03, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.27
DANN	Benign	0.63
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.029
Sift	Benign	0.56	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.033
MVP		0.18
MPC		0.10
ClinPred		0.0035	T
GERP RS		-3.4
Varity_R		0.030
gMVP		0.073

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: rs116781265; hg19: chr10-45473178;