Genetic Variant DRAM1:p.Asn37Ile (chr12-101877899-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018370.3(DRAM1):c.110A>T(p.Asn37Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000481 in 1,539,044 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

DRAM1
NM_018370.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3503551).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018370.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRAM1	NM_018370.3	MANE Select	c.110A>T	p.Asn37Ile	missense	Exon 1 of 7	NP_060840.2	Q8N682-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRAM1	ENST00000258534.13	TSL:1 MANE Select	c.110A>T	p.Asn37Ile	missense	Exon 1 of 7	ENSP00000258534.8	Q8N682-1
DRAM1	ENST00000549365.1	TSL:3	n.101A>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000447171.1	H0YHJ0
DRAM1	ENST00000963725.1		c.110A>T	p.Asn37Ile	missense	Exon 1 of 8	ENSP00000633784.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000332

AC:

AN:

150764

AF XY:

0.0000497

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000675

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000505

AC:

AN:

1387040

Hom.:

Cov.:

AF XY:

0.0000438

AC XY:

AN XY:

684716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31474

American (AMR)

AF:

0.0000286

AC:

AN:

35024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24924

East Asian (EAS)

AF:

0.00

AC:

AN:

35180

South Asian (SAS)

AF:

0.00

AC:

AN:

77864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.0000625

AC:

AN:

1071714

Other (OTH)

AF:

0.0000349

AC:

AN:

57344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41374

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Benign

0.011

Eigen_PC

Benign

0.063

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.82

M_CAP

Benign

0.024

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

3.6

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.17

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.025

Polyphen

0.47

Vest4

0.47

MutPred

0.67

Loss of sheet (P = 0.0817)

MVP

0.37

MPC

1.1

ClinPred

0.49

GERP RS

3.7

PromoterAI

0.054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.51

gMVP

0.60

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over