Variant 12-101914213-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018370.3(DRAM1):c.560A>C(p.Glu187Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,608,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DRAM1
NM_018370.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01

Variant links:

Genes affected

DRAM1 (HGNC:25645): (DNA damage regulated autophagy modulator 1) This gene is regulated as part of the p53 tumor suppressor pathway. The gene encodes a lysosomal membrane protein that is required for the induction of autophagy by the pathway. Decreased transcriptional expression of this gene is associated with various tumors. This gene has a pseudogene on chromosome 4. [provided by RefSeq, Jul 2008]

DRAM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.36913538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DRAM1	NM_018370.3 linkuse as main transcript	c.560A>C	p.Glu187Ala	missense_variant	5/7	ENST00000258534.13
DRAM1	XM_005269004.3 linkuse as main transcript	c.560A>C	p.Glu187Ala	missense_variant	5/6
DRAM1	XM_047429098.1 linkuse as main transcript	c.386A>C	p.Glu129Ala	missense_variant	5/7
DRAM1	XM_005269005.3 linkuse as main transcript	c.343-5896A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRAM1	ENST00000258534.13 linkuse as main transcript	c.560A>C	p.Glu187Ala	missense_variant	5/7	1	NM_018370.3	P1	Q8N682-1
DRAM1	ENST00000549066.1 linkuse as main transcript	c.92A>C	p.Glu31Ala	missense_variant	2/3	3
DRAM1	ENST00000544152.5 linkuse as main transcript	c.343-7003A>C		intron_variant		2			Q8N682-2
DRAM1	ENST00000551403.1 linkuse as main transcript	c.*37A>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456350

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724624

show subpopulations

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2023

The c.560A>C (p.E187A) alteration is located in exon 5 (coding exon 5) of the DRAM1 gene. This alteration results from a A to C substitution at nucleotide position 560, causing the glutamic acid (E) at amino acid position 187 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Benign

-0.055

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

M_CAP

Benign

0.0062

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.20

Sift

Benign

0.038

Sift4G

Benign

0.14

Polyphen

0.13

Vest4

0.40

MutPred

0.51

Gain of helix (P = 0.0225);

MVP

0.28

MPC

0.98

ClinPred

0.88

GERP RS

5.4

Varity_R

0.13

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over