NM_001002862.3:c.248G>A

Variant names:

• chr22-23838431-C-T
• NM_001002862.3:c.248G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001002862.3(DERL3):​c.248G>A​(p.Arg83His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000028 (0 hom.)
• Consequence: DERL3 NM_001002862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

Genes affected

DERL3 (HGNC:14236): (derlin 3) The protein encoded by this gene belongs to the derlin family, and resides in the endoplasmic reticulum (ER). Proteins that are unfolded or misfolded in the ER must be refolded or degraded to maintain the homeostasis of the ER. This protein appears to be involved in the degradation of misfolded glycoproteins in the ER. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DERL3	NM_001002862.3	c.248G>A	p.Arg83His	missense_variant	Exon 4 of 7	ENST00000318109.12	NP_001002862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DERL3	ENST00000318109.12	c.248G>A	p.Arg83His	missense_variant	Exon 4 of 7	1	NM_001002862.3	ENSP00000315303.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452254 Hom.: 0 Cov.: 35 AF XY: 0.00000416 AC XY: 3 AN XY: 721490

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

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	0.23
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.42	.;T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.9	H;H;H
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.034	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.91
MutPred		0.54		Gain of catalytic residue at L85 (P = 0.0467);Gain of catalytic residue at L85 (P = 0.0467);Gain of catalytic residue at L85 (P = 0.0467);
MVP		0.79
MPC		0.57
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.94
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr22-24180618;