rs137941190

Variant names:

• chr11-126345546-C-A
• NM_014026.6:c.947C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-126345546-C-A
• chr11-126345546-C-G
• chr11-126345546-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014026.6(DCPS):​c.947C>A​(p.Thr316Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DCPS NM_014026.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

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]

GSEC (HGNC:48645): (G-quadruplex forming sequence containing lncRNA)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCPS	NM_014026.6	c.947C>A	p.Thr316Lys	missense_variant	Exon 6 of 6	ENST00000263579.5	NP_054745.1
DCPS	NM_001350236.2	c.968C>A	p.Thr323Lys	missense_variant	Exon 6 of 6		NP_001337165.1
GSEC	NR_033839.1	n.147-3224G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCPS	ENST00000263579.5	c.947C>A	p.Thr316Lys	missense_variant	Exon 6 of 6	1	NM_014026.6	ENSP00000263579.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.3	D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0050	D;.
Polyphen		0.94	P;.
Vest4		0.50
MutPred		0.70		Gain of sheet (P = 0.0221);.;
MVP		0.67
MPC		0.19
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.69
gMVP		0.93

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: chr11-126215441;