11-126304117-C-G

Variant names:

• chr11-126304117-C-G
• rs201108066
• NM_014026.6:c.37C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014026.6(DCPS):​c.37C>G​(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R13S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCPS NM_014026.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014026.6. 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
	DCPS	NM_014026.6	MANE Select	c.37C>G	p.Arg13Gly	missense	Exon 1 of 6	NP_054745.1	A0A384MTI8
	DCPS	NM_001350236.2		c.37C>G	p.Arg13Gly	missense	Exon 1 of 6	NP_001337165.1
	TIRAP-AS1	NR_187383.1		n.115+91G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCPS	ENST00000263579.5	TSL:1 MANE Select	c.37C>G	p.Arg13Gly	missense	Exon 1 of 6	ENSP00000263579.4	Q96C86
	DCPS	ENST00000861222.1		c.37C>G	p.Arg13Gly	missense	Exon 1 of 6	ENSP00000531281.1
	DCPS	ENST00000912051.1		c.37C>G	p.Arg13Gly	missense	Exon 1 of 6	ENSP00000582110.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.20
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.22
Sift	Benign	0.042	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.18		Gain of loop (P = 0.0321)
MVP		0.66
MPC		0.46
ClinPred		0.97	D
GERP RS		5.8
PromoterAI		-0.13	Neutral
Varity_R		0.27
gMVP		0.47
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs201108066; hg19: chr11-126174012;