11-126304143-C-G

Variant names:

• chr11-126304143-C-G
• rs3740915
• NM_014026.6:c.63C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014026.6(DCPS):​c.63C>G​(p.His21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,710 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DCPS NM_014026.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

DCPS (HGNC:29812): (decapping enzyme, scavenger) This gene encodes a member of the histidine triad family of pyrophosphatases that removes short mRNA fragments containing the 5′ mRNA cap structure, which appear in the 3′ → 5′ mRNA decay pathway, following deadenylation and exosome-mediated turnover. This enzyme hydrolyzes the triphosphate linkage of the cap structure (7-methylguanosine nucleoside triphosphate) to yield 7-methylguanosine monophosphate and nucleoside diphosphate. It protects the cell from the potentially toxic accumulation of these short, capped mRNA fragments, and regulates the activity of other cap-binding proteins, which are inhibited by their accumulation. It also acts as a transcript-specific modulator of pre-mRNA splicing and microRNA turnover. [provided by RefSeq, Apr 2017]

TIRAP-AS1 (HGNC:56069): (TIRAP antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047836423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCPS	NM_014026.6	c.63C>G	p.His21Gln	missense_variant	Exon 1 of 6	ENST00000263579.5	NP_054745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCPS	ENST00000263579.5	c.63C>G	p.His21Gln	missense_variant	Exon 1 of 6	1	NM_014026.6	ENSP00000263579.4
TIRAP-AS1	ENST00000693424.1	n.157G>C		non_coding_transcript_exon_variant	Exon 1 of 1
TIRAP-AS1	ENST00000524964.2	n.116+65G>C		intron_variant	Intron 1 of 1	2
TIRAP-AS1	ENST00000691542.1	n.114+65G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250802 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135688

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.2
DANN	Benign	0.55
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.021
Sift	Benign	0.28	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.088		Gain of solvent accessibility (P = 0.0837);
MVP		0.12
MPC		0.11
ClinPred		0.056	T
GERP RS		-1.9
Varity_R		0.076
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs3740915; hg19: chr11-126174038;