rs774126957

Variant names:

• chr12-101877899-A-C
• NM_018370.3:c.110A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-101877899-A-C
• chr12-101877899-A-G
• chr12-101877899-A-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.110A>C​(p.Asn37Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000721 in 1,387,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DRAM1 NM_018370.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

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=0.25222754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRAM1	NM_018370.3	c.110A>C	p.Asn37Thr	missense_variant	Exon 1 of 7	ENST00000258534.13	NP_060840.2
DRAM1	XM_005269004.3	c.110A>C	p.Asn37Thr	missense_variant	Exon 1 of 6		XP_005269061.1
DRAM1	XM_005269005.3	c.110A>C	p.Asn37Thr	missense_variant	Exon 1 of 5		XP_005269062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRAM1	ENST00000258534.13	c.110A>C	p.Asn37Thr	missense_variant	Exon 1 of 7	1	NM_018370.3	ENSP00000258534.8
DRAM1	ENST00000549365.1	n.101A>C		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000447171.1
DRAM1	ENST00000544152.5	c.110A>C	p.Asn37Thr	missense_variant	Exon 1 of 4	2		ENSP00000445827.1
DRAM1	ENST00000551403.1	n.110A>C		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000448075.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387040 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.00073
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.077
Sift	Uncertain	0.0080	D;T
Sift4G	Benign	0.14	T;T
Polyphen		0.42	B;.
Vest4		0.30
MutPred		0.58		Gain of phosphorylation at N37 (P = 0.0958);Gain of phosphorylation at N37 (P = 0.0958);
MVP		0.43
MPC		0.89
ClinPred		0.66	D
GERP RS		3.7
Varity_R		0.19
gMVP		0.42

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: chr12-102271677;