rs148625091

Variant names:

• chr5-141925433-C-G
• rs148625091
• NM_014773.5:c.170C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-141925433-C-G
• chr5-141925433-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014773.5(DELE1):​c.170C>G​(p.Thr57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,443,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T57M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DELE1 NM_014773.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801
• Publications: 0 publications found

Genes affected

DELE1 (HGNC:28969): (DAP3 binding cell death enhancer 1) Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in HRI-mediated signaling; extrinsic apoptotic signaling pathway via death domain receptors; and regulation of cysteine-type endopeptidase activity involved in apoptotic process. Located in cytosol and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040878236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014773.5. 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
	DELE1	NM_014773.5	MANE Select	c.170C>G	p.Thr57Arg	missense	Exon 3 of 12	NP_055588.3
	DELE1	NM_001142603.3		c.170C>G	p.Thr57Arg	missense	Exon 3 of 13	NP_001136075.1	Q14154

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DELE1	ENST00000432126.7	TSL:1 MANE Select	c.170C>G	p.Thr57Arg	missense	Exon 3 of 12	ENSP00000396225.2	Q14154
	DELE1	ENST00000959462.1		c.170C>G	p.Thr57Arg	missense	Exon 3 of 13	ENSP00000629521.1
	DELE1	ENST00000959463.1		c.170C>G	p.Thr57Arg	missense	Exon 3 of 12	ENSP00000629522.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1443690 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 718052

African (AFR) AF: 0.00 AC: 0 AN: 32240

American (AMR) AF: 0.00 AC: 0 AN: 42128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 37888

South Asian (SAS) AF: 0.00 AC: 0 AN: 83694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1103552

Other (OTH) AF: 0.00 AC: 0 AN: 59672

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.8
DANN	Benign	0.49
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.80
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.028
Sift	Benign	0.56	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.14		Loss of phosphorylation at T57 (P = 0.0161)
MVP		0.076
MPC		0.19
ClinPred		0.018	T
GERP RS		0.19
Varity_R		0.099
gMVP		0.27
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148625091; hg19: chr5-141304998; COSMIC: COSV105852247; COSMIC: COSV105852247;