12-101901342-C-T

Variant names:

• chr12-101901342-C-T
• NM_018370.3:c.251C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018370.3(DRAM1):​c.251C>T​(p.Thr84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DRAM1 NM_018370.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069064885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRAM1	NM_018370.3	c.251C>T	p.Thr84Ile	missense_variant	Exon 3 of 7	ENST00000258534.13	NP_060840.2
DRAM1	XM_005269004.3	c.251C>T	p.Thr84Ile	missense_variant	Exon 3 of 6		XP_005269061.1
DRAM1	XM_047429098.1	c.77C>T	p.Thr26Ile	missense_variant	Exon 3 of 7		XP_047285054.1
DRAM1	XM_005269005.3	c.251C>T	p.Thr84Ile	missense_variant	Exon 3 of 5		XP_005269062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRAM1	ENST00000258534.13	c.251C>T	p.Thr84Ile	missense_variant	Exon 3 of 7	1	NM_018370.3	ENSP00000258534.8
DRAM1	ENST00000549365.1	n.*238C>T		non_coding_transcript_exon_variant	Exon 4 of 5	3		ENSP00000447171.1
DRAM1	ENST00000549365.1	n.*238C>T		3_prime_UTR_variant	Exon 4 of 5	3		ENSP00000447171.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.052
Sift	Benign	0.18	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.45		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.25
MPC		0.82
ClinPred		0.16	T
GERP RS		3.8
Varity_R		0.087
gMVP		0.21

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: chr12-102295120;